El objetivo principal de nuestro laboratorio es entender los mecanismos moleculares que subyacen (i) a la patogenicidad bacteriana y (ii) a la respuesta del sistema inmune contra proteínas inmunogénicas. Queremos entender:

1. Como Brucella y otras bacterias infectivas son capaces de sensar las claves ambientales (tensión de oxígeno, potenciales redox, luz, etc.)?
2. Cuales de las adaptaciones metabólicas de Brucella son importantes para generar una infección efectiva en el hospedador y como podemos manipularlas para interrumpir el proceso infeccioso?
3. Como los factores de virulencia de Brucella afectan la interacción hospedador-microbio?
4. Cuales son las bases moleculares y celulares que explican la inmunogenicidad de la Lumazina Sintasa de Brucella (BLS)?
5. Podemos crear vacunas terapéuticas y protectivas usando ingeniería de proteínas sobre la estructura de BLS?

 

El carácter multidisciplinario del grupo de trabajo permite abarcar diversos aspectos de los temas de investigación. Uno de los temas de estudio del laboratorio es el metabolismo de flavinas y el rol de flavoproteínas en Brucella y otros Rhizobiales. Descubrimos que algunas enzimas del metabolismo de flavinas constituyen factores de virulencia que actúan en el nicho replicativo de la bacteria, y que Brucella tiene un metabolismo de síntesis de flavinas atípico. Investigamos en forma general el rol de la biosíntesis de flavinas en la adaptación metabólica que sufre este patógeno intracelular en su nicho replicativo pobre en nutrientes y en oxígeno. Nuestra principal pregunta es cómo se adapta Brucella a condiciones de falta de nutrientes y de oxígeno y logra multiplicarse exitosamente, y si las flavinas y flavoproteínas juegan un rol importante en dicha adaptación y en el sensado de señales externas tales como la luz, la tensión de oxígeno y otras. Estudiamos además una flavoproteína de Brucella, LOV-HK, que es capaz de sensar la luz azul y de esa manera modula la virulencia de la bacteria. Por otro lado, estudiamos las características inmunológicas de una proteína polimérica de Brucella, la lumazina sintetasa (BLS) al ser utilizada como carrier vacunal y el rol de receptores de tipo Toll en dicha respuesta. Algunas de las técnicas que se realizan:

• Mutaciones y deleciones de genes de interés, y complementación de las mismas.
• Caracterización del la regulación transcripcional y traduccional de los genes de interés.
• Estudio de la actividad bioquímica de las enzimas de la vía metabólica de las flavinas.
• Estudio de la actividad bioquímica de las flavoproteínas sensoras y sus mecanismos de transducción de señales.
• Estudios de estructura/función de proteínas mediante cristalografía de Rayos y RMN.
• Estudio de interacción proteína-proteína in vitro mediante técnicas biofísicas y display en fagos.
• Estudio de interacción proteína-proteína in vivo mediante técnicas de doble híbrido bacteriano.
• Estudios microbiológicos de crecimiento bacteriano.
• Estudios in vitro en cultivos primarios y líneas celulares.
• Estudios inmunológicos básicos y de infección en el modelo murino.
• Utilización de microscopía de fluorescencia y confocal.

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2019

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The reaction mechanism of metallo-beta-lactamases is tuned by the conformation of an active site mobile loop. Antimicrobial Agents and Chemotherapy Palacios, A.R., Mojica, M.F., Giannini, E., Taracila, M.A., Bethel, C.R., Alzari, P.M., Otero, L.H., Klinke, S., Llarrull, L.I., Bonomi, R.A. & Vila, A.J. (2019)., en prensa.

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Asymmetric bifunctional protein nanoparticles through redesign of self-assembly. Santiago Sosa, Andrés H. Rossi, Alan M. Szalai, Sebastián Klinke, Jimena Rinaldi, Ana Farias, Paula M. Berguer, Alejandro D. Nadra, Fernando D. Stefani, Fernando A. Goldbaum, Hernán R. Bonomi (2019). Nanoscale Advances, en prensa. DOI:10.1039/C8NA00375K

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Characterization of folding-sensitive nanobodies as tools to study the expression and quality of protein particle immunogens. Alzogaray V, Urrutia M, Berguer P, Rossi A, Zylberman V, Pardo R, Bonomi HR, Goldbaum FA.  J Biotechnol. 2019 Jan 25. pii: S0168-1656(19)30005-7. doi: 10.1016/j.jbiotec.2019.01.001. PubMed PMID: 30690101. 

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Recombinant flagellins with deletions in domains D1, D2, and D3: Characterization as novel immunoadjuvants. Vaccine. Biedma ME, Cayet D, Tabareau J, Rossi AH, Ivičak-Kocjan K, Moreno G, Errea A, Soulard D, Parisi G, Jerala R, Berguer P, Rumbo M, Sirard JC.  2019 Jan 21;37(4):652-663. doi:10.1016/j.vaccine.2018.12.009. Epub 2018 Dec 21. PubMed PMID: 30583910.

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2018

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Crystallization and initial X-ray diffraction analysis of the multi-domain Brucella blue light-activated histidine kinase LOV-HK in its illuminated state. Rinaldi, J., Fernández, I., Poth, L.M., Shepard, W.E., Savko, M., Goldbaum, F.A. & Klinke, S. (2018).  Biochemistry and Biophysics Reports 16, 39-43.

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Engineering a bifunctional copper site in the cupredoxin fold by loop-directed mutagenesis. Espinoza-Cara, A., Zitare, U., Alvarez-Paggi, D., Klinke, S., Otero, L.H., Murgida, D.H. & Vila, A.J. (2018). Chemical Science 9, 6692-6702.  

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Draft genome sequence of Methylobacterium sp. strain V23, isolated from accretion ice of the Antarctic subglacial Lake Vostok. Sapp, A., Huguet-Tapia, J.C., Sánchez-Lamas, M., Antelo, G.T., Primo, E.D., Rinaldi, J., Klinke, S., Goldbaum, F.A., Bonomi, H.R., Christner, B.C. & Otero, L.H. (2018). Genome Announcements 6, e00145-18.

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The disruptive effect of lysozyme on the bacterial cell wall explored by an in-silico structural outlook: a comprehensive laboratory exercise. Primo, E.D., Otero, L., Ruiz, F., Klinke, S. & Giordano, W. (2018).  Biochemistry and Molecular Biology Education 46, 83-90.

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Conformational plasticity of the intrinsically disordered protein ASR1 modulates its function as a drought stress-responsive gene. Wetzler DE, Fuchs Wightman F, Bucci HA, Rinaldi J, Caramelo JJ, Iusem ND, Ricardi MM. PLoS One. 2018 Aug 23;13(8):e0202808. doi: 10.1371/journal.pone.0202808. eCollection 2018. PubMed PMID: 30138481; PubMed Central PMCID: PMC6107238.

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Acidic pH triggers the phosphorylation of the response regulator NtrX in alphaproteobacteria. Fernández I, Sycz G, Goldbaum FA, Carrica MDC. PLoS One. 2018 Apr 10;13(4):e0194486. doi: 10.1371.

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E. EcXyl43 β-xylosidase: molecular modeling, activity on natural and artificial substrates, and synergism with endoxylanases for lignocellulose deconstruction Ontañon, O.M., Ghio, S., Marrero Díaz de Villegas, R., Piccinni, F.E., Talia, P.M., Cerutti, M.L., Campos,  Appl. Microbiol. Biotechnol. 2018 102(16), 6959-6971. doi: 10.1007/s00253-018-9138-7.  

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2017

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The superfamily keeps growing: Identification in trypanosomatids of RibJ, the first riboflavin transporter family in protists.

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Characterization of structural and immunological properties of a fusion protein between flagellin from Salmonella and lumazine synthase from Brucella.

PMID:28257593

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Polymeric antigen BLSOmp31 in aluminium hydroxide induces serum bactericidal and opsonic antibodies against Brucella canis in dogs.

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Three-Dimensional Structure of Full-Length NtrX, an Unusual Member of the NtrC Family of Response Regulators.

2016

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 Structural and functional characterization of a cold adapted TPM-domain with ATPase/ADPase activity.

Development of camelid single chain antibodies against Shiga toxin type 2 (Stx2) with therapeutic potential against Hemolytic Uremic Syndrome (HUS).

Mejías MP, Hiriart Y, Lauché C, Fernández-Brando RJ, Pardo R, Bruballa A, Ramos MV, Goldbaum FA, Palermo MS, Zylberman V.

Sci Rep. 2016 Apr 27;6:24913. doi: 10.1038/srep24913.

PMID:27118524

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Structure of the Full-Length Bacteriophytochrome from the Plant Pathogen Xanthomonas campestris Provides Clues to its Long-Range Signaling Mechanism.

Otero LH, Klinke S, Rinaldi J, Velázquez-Escobar F, Mroginski MA, Fernández López M, Malamud F, Vojnov AA, Hildebrandt P, Goldbaum FA, Bonomi HR.

J Mol Biol. 2016 Sep 25;428(19):3702-20. doi: 10.1016/j.jmb.2016.04.012. Epub 2016 Apr 20.

PMID:27107635

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Spray dried microspheres based on chitosan: A promising new carrier for intranasal administration of polymeric antigen BLSOmp31 for prevention of ovine brucellosis.

Díaz AG, Quinteros DA, Llabot JM, Palma SD, Allemandi DA, Ghersi G, Zylberman V, Goldbaum FA, Estein SM.

Mater Sci Eng C Mater Biol Appl. 2016 May;62:489-96. doi: 10.1016/j.msec.2016.01.084. Epub 2016 Feb 2.

PMID:26952451

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Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain.

Rinaldi J, Arrar M, Sycz G, Cerutti ML, Berguer PM, Paris G, Estrín DA, Martí MA, Klinke S, Goldbaum FA.

J Mol Biol. 2016 Mar 27;428(6):1165-79. doi: 10.1016/j.jmb.2016.01.026. Epub 2016 Feb 2.

PMID:26851072

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2015

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Expression of the Multimeric and Highly Immunogenic Brucella spp. Lumazine Synthase Fused to Bovine Rotavirus VP8d as a Scaffold for Antigen Production in Tobacco Chloroplasts.

Alfano EF, Lentz EM, Bellido D, Dus Santos MJ, Goldbaum FA, Wigdorovitz A, Bravo-Almonacid FF.

Front Plant Sci. 2015 Dec 23;6:1170. doi: 10.3389/fpls.2015.01170. eCollection 2015.

PMID:26779198

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A bacterial protease inhibitor protects antigens delivered in oral vaccines from digestion while triggering specific mucosal immune responses.

Ibañez AE, Coria LM, Carabajal MV, Delpino MV, Risso GS, Cobiello PG, Rinaldi J, Barrionuevo P, Bruno L, Frank F, Klinke S, Goldbaum FA, Briones G, Giambartolomei GH, Pasquevich KA, Cassataro J.

J Control Release. 2015 Dec 28;220(Pt A):18-28. doi: 10.1016/j.jconrel.2015.10.011. Epub 2015 Oct 9.

PMID:26456256

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S-SAD phasing of monoclinic histidine kinase from Brucella abortus combining data from multiple crystals and orientations: an example of data-collection strategy and a posteriori analysis of different data combinations.

Klinke S, Foos N, Rinaldi JJ, Paris G, Goldbaum FA, Legrand P, Guimarães BG, Thompson A.

Acta Crystallogr D Biol Crystallogr. 2015 Jul;71(Pt 7):1433-43. doi: 10.1107/S1399004715007622. Epub 2015 Jun 30.

PMID:26143915

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Snapshots of Conformational Changes Shed Light into the NtrX Receiver Domain Signal Transduction Mechanism.

Fernández I, Otero LH, Klinke S, Carrica Mdel C, Goldbaum FA.

J Mol Biol. 2015 Oct 9;427(20):3258-72. doi: 10.1016/j.jmb.2015.06.010. Epub 2015 Jun 23.

PMID:26113057

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LOV Histidine Kinase Modulates the General Stress Response System and Affects the virB Operon Expression in Brucella abortus.

Sycz G, Carrica MC, Tseng TS, Bogomolni RA, Briggs WR, Goldbaum FA, Paris G.

PLoS One. 2015 May 19;10(5):e0124058. doi: 10.1371/journal.pone.0124058. eCollection 2015.

PMID:25993430

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Brucella spp. Lumazine Synthase Induces a TLR4-Mediated Protective Response against B16 Melanoma in Mice.

Rossi AH, Farias A, Fernández JE, Bonomi HR, Goldbaum FA, Berguer PM.

PLoS One. 2015 May 14;10(5):e0126827. doi: 10.1371/journal.pone.0126827. eCollection 2015.

PMID:25973756

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Extensive Identification of Bacterial Riboflavin Transporters and Their Distribution across Bacterial Species.

Gutiérrez-Preciado A, Torres AG, Merino E, Bonomi HR, Goldbaum FA, García-Angulo VA.

PLoS One. 2015 May 4;10(5):e0126124. doi: 10.1371/journal.pone.0126124. eCollection 2015.

PMID:25938806

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Selection of nanobodies that block the enzymatic and cytotoxic activities of the binary Clostridium difficile toxin CDT.

Unger M, Eichhoff AM, Schumacher L, Strysio M, Menzel S, Schwan C, Alzogaray V, Zylberman V, Seman M, Brandner J, Rohde H, Zhu K, Haag F, Mittrücker HW, Goldbaum F, Aktories K, Koch-Nolte F.

Sci Rep. 2015 Jan 19;5:7850. doi: 10.1038/srep07850.

PMID:25597743

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2014

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Crystallization and preliminary X-ray characterization of the full-length bacteriophytochrome from the plant pathogen Xanthomonas campestris pv. campestris.

Klinke S, Otero LH, Rinaldi J, Sosa S, Guimarães BG, Shepard WE, Goldbaum FA, Bonomi HR.

Acta Crystallogr F Struct Biol Commun. 2014 Dec 1;70(Pt 12):1636-9. doi: 10.1107/S2053230X14023243. Epub 2014 Nov 14.

PMID:25484215

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Solution and crystal structure of BA42, a protein from the Antarctic bacterium Bizionia argentinensis comprised of a stand-alone TPM domain.

Aran M, Smal C, Pellizza L, Gallo M, Otero LH, Klinke S, Goldbaum FA, Ithurralde ER, Bercovich A, Mac Cormack WP, Turjanski AG, Cicero DO.

Proteins. 2014 Nov;82(11):3062-78. doi: 10.1002/prot.24667. Epub 2014 Sep 3.

PMID:25116514

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Crystallographic and kinetic study of riboflavin synthase from Brucella abortus, a chemotherapeutic target with an enhanced intrinsic flexibility.

Serer MI, Bonomi HR, Guimarães BG, Rossi RC, Goldbaum FA, Klinke S.

Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1419-34. doi: 10.1107/S1399004714005161. Epub 2014 Apr 30.

PMID:24816110

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Protection of mice against Shiga toxin 2 (Stx2)-associated damage by maternal immunization with a Brucella lumazine synthase-Stx2 B subunit chimera.

Mejias MP, Cabrera G, Fernández-Brando RJ, Baschkier A, Ghersi G, Abrey-Recalde MJ, Miliwebsky E, Meiss R, Goldbaum F, Zylberman V, Rivas M, Palermo MS.

Infect Immun. 2014 Apr;82(4):1491-9. doi: 10.1128/IAI.00027-14. Epub 2014 Jan 13.

PMID:24421050

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2013

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Identification and characterization of RibN, a novel family of riboflavin transporters from Rhizobium leguminosarum and other proteobacteria.

García Angulo VA, Bonomi HR, Posadas DM, Serer MI, Torres AG, Zorreguieta Á, Goldbaum FA.

J Bacteriol. 2013 Oct;195(20):4611-9. doi: 10.1128/JB.00644-13. Epub 2013 Aug 9.

PMID:23935051

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Immunization with a chimera consisting of the B subunit of Shiga toxin type 2 and brucella lumazine synthase confers total protection against Shiga toxins in mice.

Mejias MP, Ghersi G, Craig PO, Panek CA, Bentancor LV, Baschkier A, Goldbaum FA, Zylberman V, Palermo MS.

J Immunol. 2013 Sep 1;191(5):2403-11. doi: 10.4049/jimmunol.1300999. Epub 2013 Aug 5.

PMID:23918978

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The vaccine candidate BLSOmp31 protects mice against Brucella canis infection.

Clausse M, Díaz AG, Ghersi G, Zylberman V, Cassataro J, Giambartolomei GH, Goldbaum FA, Estein SM.

Vaccine. 2013 Dec 9;31(51):6129-35. doi: 10.1016/j.vaccine.2013.07.041. Epub 2013 Jul 30.

PMID:23906889

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Immune response and serum bactericidal activity against Brucella ovis elicited using a short immunization schedule with the polymeric antigen BLSOmp31 in rams.

Díaz AG, Clausse M, Paolicchi FA, Fiorentino MA, Ghersi G, Zylberman V, Goldbaum FA, Estein SM.

Vet Immunol Immunopathol. 2013 Jul 15;154(1-2):36-41. doi: 10.1016/j.vetimm.2013.04.003. Epub 2013 Apr 11.

PMID:23643287

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The art of blocking ADP-ribosyltransferases (ARTs): nanobodies as experimental and therapeutic tools to block mammalian and toxin ARTs.

Menzel S, Rissiek B, Haag F, Goldbaum FA, Koch-Nolte F.

FEBS J. 2013 Aug;280(15):3543-50. doi: 10.1111/febs.12313. Epub 2013 Jun 14. Review.

PMID:23627412

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The two-component systems PrrBA and NtrYX co-ordinately regulate the adaptation of Brucella abortus to an oxygen-limited environment.

Carrica Mdel C, Fernandez I, Sieira R, Paris G, Goldbaum FA.

Mol Microbiol. 2013 Apr;88(2):222-33. doi: 10.1111/mmi.12181. Epub 2013 Mar 26.

PMID:23527685

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Tandem repeats of the extracellular domain of Matrix 2 influenza protein exposed in Brucella lumazine synthase decameric carrier molecule induce protection in mice.

Alvarez P, Zylberman V, Ghersi G, Boado L, Palacios C, Goldbaum F, Mattion N.

Vaccine. 2013 Jan 21;31(5):806-12. doi: 10.1016/j.vaccine.2012.11.072. Epub 2012 Dec 27.

PMID:23246552

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2012

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A polymeric protein induces specific cytotoxicity in a TLR4 dependent manner in the absence of adjuvants.

Berguer PM, Alzogaray VA, Rossi AH, Mundiñano J, Piazzon I, Goldbaum FA.

PLoS One. 2012;7(9):e45705. doi: 10.1371/journal.pone.0045705. Epub 2012 Sep 24.

PMID:23029192

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Light regulates attachment, exopolysaccharide production, and nodulation in Rhizobium leguminosarum through a LOV-histidine kinase photoreceptor.

Bonomi HR, Posadas DM, Paris G, Carrica Mdel C, Frederickson M, Pietrasanta LI, Bogomolni RA, Zorreguieta A, Goldbaum FA.

Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12135-40. doi: 10.1073/pnas.1121292109. Epub 2012 Jul 5.

PMID:22773814

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The NtrY/X two-component system of Brucella spp. acts as a redox sensor and regulates the expression of nitrogen respiration enzymes.

Carrica Mdel C, Fernandez I, Martí MA, Paris G, Goldbaum FA.

Mol Microbiol. 2012 Jul;85(1):39-50. doi: 10.1111/j.1365-2958.2012.08095.x. Epub 2012 May 30.

PMID:22582926

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The β-scaffold of the LOV domain of the Brucella light-activated histidine kinase is a key element for signal transduction.

Rinaldi J, Gallo M, Klinke S, Paris G, Bonomi HR, Bogomolni RA, Cicero DO, Goldbaum FA.

J Mol Biol. 2012 Jun 29;420(1-2):112-27. doi: 10.1016/j.jmb.2012.04.006. Epub 2012 Apr 11.

PMID:22504229

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Polymeric Display of Proteins through High Affinity Leucine Zipper Peptide Adaptors.

Craig PO, Alzogaray V, Goldbaum FA.

Biomacromolecules. 2012 Apr 9;13(4):1112-21. doi: 10.1021/bm201875p. Epub 2012 Mar 20.

PMID:22372794

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2011

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Heterologous prime-boost oral immunization with GK-1 peptide from Taenia crassiceps cysticerci induces protective immunity.

Fragoso G, Esquivel-Guadarrama F, Santana MA, Bobes RJ, Hernández B, Cervantes J, Segura R, Goldbaum FA, Sciutto E, Rosas G.

Clin Vaccine Immunol. 2011 Jul;18(7):1067-76. doi: 10.1128/CVI.05030-11. Epub 2011 May 18.

PMID:21593234

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YqiC of Salmonella enterica serovar Typhimurium is a membrane fusogenic protein required for mice colonization.

Carrica MC, Craig PO, García-Angulo VA, Aguirre A, García-Véscovi E, Goldbaum FA, Cravero SL.

BMC Microbiol. 2011 May 9;11:95. doi: 10.1186/1471-2180-11-95.

PMID:21554724

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Sensing the dissociation of a polymeric enzyme by means of an engineered intrinsic probe.

Ainciart N, Zylberman V, Craig PO, Nygaard D, Bonomi HR, Cauerhff AA, Goldbaum FA.

Proteins. 2011 Apr;79(4):1079-88. doi: 10.1002/prot.22945. Epub 2011 Jan 18.

PMID:21246631

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Single-domain llama antibodies as specific intracellular inhibitors of SpvB, the actin ADP-ribosylating toxin of Salmonella typhimurium.

Alzogaray V, Danquah W, Aguirre A, Urrutia M, Berguer P, García Véscovi E, Haag F, Koch-Nolte F, Goldbaum FA.

FASEB J. 2011 Feb;25(2):526-34. doi: 10.1096/fj.10-162958. Epub 2010 Oct 12.

PMID:20940265

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2010

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An atypical riboflavin pathway is essential for Brucella abortus virulence.

Bonomi HR, Marchesini MI, Klinke S, Ugalde JE, Zylberman V, Ugalde RA, Comerci DJ, Goldbaum FA.

PLoS One. 2010 Feb 25;5(2):e9435. doi: 10.1371/journal.pone.0009435.

PMID:20195542

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Single domain antibodies are specially suited for quantitative determination of gliadins under denaturing conditions.

Doña V, Urrutia M, Bayardo M, Alzogaray V, Goldbaum FA, Chirdo FG.

J Agric Food Chem. 2010 Jan 27;58(2):918-26. doi: 10.1021/jf902973c.

PMID:20039674

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2009

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The polymeric antigen BLSOmp31 confers protection against Brucella ovis infection in rams.

Estein SM, Fiorentino MA, Paolicchi FA, Clausse M, Manazza J, Cassataro J, Giambartolomei GH, Coria LM, Zylberman V, Fossati CA, Kjeken R, Goldbaum FA.

Vaccine. 2009 Nov 12;27(48):6704-11. doi: 10.1016/j.vaccine.2009.08.097. Epub 2009 Sep 11.

PMID:19748579

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Single domain antibodies: promising experimental and therapeutic tools in infection and immunity.

Wesolowski J, Alzogaray V, Reyelt J, Unger M, Juarez K, Urrutia M, Cauerhff A, Danquah W, Rissiek B, Scheuplein F, Schwarz N, Adriouch S, Boyer O, Seman M, Licea A, Serreze DV, Goldbaum FA, Haag F, Koch-Nolte F.

Med Microbiol Immunol. 2009 Aug;198(3):157-74. doi: 10.1007/s00430-009-0116-7. Epub 2009 Jun 16. Review.

PMID:19529959

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Brucella spp. lumazine synthase as a bovine rotavirus antigen delivery system.

Bellido D, Craig PO, Mozgovoj MV, Gonzalez DD, Wigdorovitz A, Goldbaum FA, Dus Santos MJ.

Vaccine. 2009 Jan 1;27(1):136-45. doi: 10.1016/j.vaccine.2008.10.018. Epub 2008 Oct 28.

PMID:18973781

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2008

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Relevance of the diversity among members of the Trypanosoma cruzi trans-sialidase family analyzed with camelids single-domain antibodies.

Ratier L, Urrutia M, Paris G, Zarebski L, Frasch AC, Goldbaum FA.

PLoS One. 2008;3(10):e3524. doi: 10.1371/journal.pone.0003524. Epub 2008 Oct 24.

PMID:18949046

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Brucella abortus MFP: a trimeric coiled-coil protein with membrane fusogenic activity.

Carrica Mdel C, Craig PO, Alonso Sdel V, Goldbaum FA, Cravero SL.

Biochemistry. 2008 Aug 5;47(31):8165-75. doi: 10.1021/bi800462y. Epub 2008 Jul 11.

PMID:18616282

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Structure of the mature ectodomain of the human receptor-type protein-tyrosine phosphatase IA-2.

Primo ME, Klinke S, Sica MP, Goldbaum FA, Jakoncic J, Poskus E, Ermácora MR.

J Biol Chem. 2008 Feb 22;283(8):4674-81. Epub 2007 Nov 29.

PMID:18048354

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2007

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Renewed hope for a vaccine against the intestinal adult Taenia solium.

Sciutto E, Rosas G, Cruz-Revilla C, Toledo A, Cervantes J, Hernández M, Hernándezt B, Goldbaum FA, de Aluja AS, Fragoso G, Larralde C.

J Parasitol. 2007 Aug;93(4):824-31. Review.

PMID:17918361

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Affinity maturation increases the stability and plasticity of the Fv domain of anti-protein antibodies.

Acierno JP, Braden BC, Klinke S, Goldbaum FA, Cauerhff A.

J Mol Biol. 2007 Nov 16;374(1):130-46. Epub 2007 Sep 11.

PMID:17916365

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Structural and kinetic properties of lumazine synthase isoenzymes in the order Rhizobiales.

Klinke S, Zylberman V, Bonomi HR, Haase I, Guimarães BG, Braden BC, Bacher A, Fischer M, Goldbaum FA.

J Mol Biol. 2007 Oct 26;373(3):664-80. Epub 2007 Aug 21.

PMID:17854827

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Blue-light-activated histidine kinases: two-component sensors in bacteria.

Swartz TE, Tseng TS, Frederickson MA, Paris G, Comerci DJ, Rajashekara G, Kim JG, Mudgett MB, Splitter GA, Ugalde RA, Goldbaum FA, Briggs WR, Bogomolni RA.

Science. 2007 Aug 24;317(5841):1090-3.

PMID:17717187

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A DNA vaccine coding for the chimera BLSOmp31 induced a better degree of protection against B. ovis and a similar degree of protection against B. melitensis than Rev.1 vaccination.

Cassataro J, Pasquevich KA, Estein SM, Laplagne DA, Zwerdling A, de la Barrera S, Bowden R, Fossati CA, Giambartolomei GH, Goldbaum FA.

Vaccine. 2007 Aug 10;25(32):5958-67. Epub 2007 Jun 12.

PMID:17600596

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Single domain antibodies from llama effectively and specifically block T cell ecto-ADP-ribosyltransferase ART2.2 in vivo.

Koch-Nolte F, Reyelt J, Schössow B, Schwarz N, Scheuplein F, Rothenburg S, Haag F, Alzogaray V, Cauerhff A, Goldbaum FA.

FASEB J. 2007 Nov;21(13):3490-8. Epub 2007 Jun 15.

PMID:17575259

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Specific recognition of a DNA immunogen by its elicited antibody.

Sanguineti S, Centeno Crowley JM, Lodeiro Merlo MF, Cerutti ML, Wilson IA, Goldbaum FA, Stanfield RL, de Prat-Gay G.

J Mol Biol. 2007 Jun 29;370(1):183-95. Epub 2007 Apr 24.

PMID:17512945

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A recombinant subunit vaccine based on the insertion of 27 amino acids from Omp31 to the N-terminus of BLS induced a similar degree of protection against B. ovis than Rev.1 vaccination.

Cassataro J, Pasquevich KA, Estein SM, Laplagne DA, Velikovsky CA, de la Barrera S, Bowden R, Fossati CA, Giambartolomei GH, Goldbaum FA.

Vaccine. 2007 May 30;25(22):4437-46. Epub 2007 Apr 2.

PMID:17442465

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Improvement of the synthetic tri-peptide vaccine (S3Pvac) against porcine Taenia solium cysticercosis in search of a more effective, inexpensive and manageable vaccine.

Sciutto E, Rosas G, Hernández M, Morales J, Cruz-Revilla C, Toledo A, Manoutcharian K, Gevorkian G, Blancas A, Acero G, Hernández B, Cervantes J, Bobes RJ, Goldbaum FA, Huerta M, Diaz-Orea A, Fleury A, de Aluja AS, Cabrera-Ponce JL, Herrera-Estrella L, Fragoso G, Larralde C.

Vaccine. 2007 Feb 9;25(8):1368-78. Epub 2006 Oct 23. Review.

PMID:17188784

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2006

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Antibody recognition of a flexible epitope at the DNA binding site of the human papillomavirus transcriptional regulator E2.

Cerutti ML, Ferreiro DU, Sanguineti S, Goldbaum FA, de Prat-Gay G.

Biochemistry. 2006 Dec 26;45(51):15520-8.

PMID:17176073

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Effective protection against experimental Taenia solium tapeworm infection in hamsters by primo-infection and by vaccination with recombinant or synthetic heterologous antigens.

Cruz-Revilla C, Toledo A, Rosas G, Huerta M, Flores-Perez I, Peña N, Morales J, Cisneros-Quiñones J, Meneses G, Díaz-Orea A, Anciart N, Goldbaum F, Aluja A, Larralde C, Fragoso G, Sciutto E.

J Parasitol. 2006 Aug;92(4):864-7.

PMID:16995407

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Evolution of vitamin B2 biosynthesis: 6,7-dimethyl-8-ribityllumazine synthases of Brucella.

Zylberman V, Klinke S, Haase I, Bacher A, Fischer M, Goldbaum FA.

J Bacteriol. 2006 Sep;188(17):6135-42.

PMID:16923880

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Brucella spp. lumazine synthase: a novel adjuvant and antigen delivery system to effectively induce oral immunity.

Rosas G, Fragoso G, Ainciart N, Esquivel-Guadarrama F, Santana A, Bobes RJ, Ramírez-Pliego O, Toledo A, Cruz-Revilla C, Meneses G, Berguer P, Goldbaum FA, Sciutto E.

Microbes Infect. 2006 Apr;8(5):1277-86. Epub 2006 Feb 7.

PMID:16697684

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Exploring protein interfaces with a general photochemical reagent.

Gómez GE, Cauerhff A, Craig PO, Goldbaum FA, Delfino JM. Protein Sci. 2006 Apr;15(4):744-52. PMID:16600965

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Brucella outer membrane protein Omp31 is a haemin-binding protein.

Delpino MV, Cassataro J, Fossati CA, Goldbaum FA, Baldi PC.

Microbes Infect. 2006 Apr;8(5):1203-8. Epub 2006 Jan 19.

PMID:16517201

---

A polymeric bacterial protein activates dendritic cells via TLR4.

Berguer PM, Mundiñano J, Piazzon I, Goldbaum FA.

J Immunol. 2006 Feb 15;176(4):2366-72.

PMID:16455994

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2005-2000

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Multiple display of a protein domain on a bacterial polymeric scaffold.

Craig PO, Berguer PM, Ainciart N, Zylberman V, Thomas MG, Martinez Tosar LJ, Bulloj A, Boccaccio GL, Goldbaum FA.

Proteins. 2005 Dec 1;61(4):1089-100.

PMID:16193482

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Crystallographic studies on decameric Brucella spp. Lumazine synthase: a novel quaternary arrangement evolved for a new function?

Klinke S, Zylberman V, Vega DR, Guimarães BG, Braden BC, Goldbaum FA.

J Mol Biol. 2005 Oct 14;353(1):124-37.

PMID:16165152

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Llama single domain antibodies as a tool for molecular mimicry.

Zarebski LM, Urrutia M, Goldbaum FA.

J Mol Biol. 2005 Jun 17;349(4):814-24. Epub 2005 Apr 21.

PMID:15890359

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Brucella spp. lumazine synthase: a novel antigen delivery system.

Sciutto E, Toledo A, Cruz C, Rosas G, Meneses G, Laplagne D, Ainciart N, Cervantes J, Fragoso G, Goldbaum FA.

Vaccine. 2005 Apr 15;23(21):2784-90.

PMID:15780726

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A viral DNA-binding domain elicits anti-DNA antibodies of different specificities.

Cerutti ML, Zarebski LM, de Prat Gay G, Goldbaum FA.

Mol Immunol. 2005 Feb;42(3):327-33.

PMID:15589321

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Engineering of a polymeric bacterial protein as a scaffold for the multiple display of peptides.

Laplagne DA, Zylberman V, Ainciart N, Steward MW, Sciutto E, Fossati CA, Goldbaum FA.

Proteins. 2004 Dec 1;57(4):820-8.

PMID:15390265

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Structural mechanism for affinity maturation of an anti-lysozyme antibody.

Cauerhff A, Goldbaum FA, Braden BC.

Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3539-44. Epub 2004 Feb 26.

PMID:14988501

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High order quaternary arrangement confers increased structural stability to Brucella sp. lumazine synthase.

Zylberman V, Craig PO, Klinke S, Braden BC, Cauerhff A, Goldbaum FA.

J Biol Chem. 2004 Feb 27;279(9):8093-101. Epub 2003 Dec 1.

PMID:14660615

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Sequence determinants of quaternary structure in lumazine synthase.

Fornasari MS, Laplagne DA, Frankel N, Cauerhff AA, Goldbaum FA, Echave J.

Mol Biol Evol. 2004 Jan;21(1):97-107. Epub 2003 Oct 1.

PMID:14523158

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Brucella lumazine synthase elicits a mixed Th1-Th2 immune response and reduces infection in mice challenged with Brucella abortus 544 independently of the adjuvant formulation used.

Velikovsky CA, Goldbaum FA, Cassataro J, Estein S, Bowden RA, Bruno L, Fossati CA, Giambartolomei GH.

Infect Immun. 2003 Oct;71(10):5750-5.

PMID:14500496

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Specific antibody-DNA interaction: a novel strategy for tight DNA recognition.

Di Pietro SM, Centeno JM, Cerutti ML, Lodeiro MF, Ferreiro DU, Alonso LG, Schwarz FP, Goldbaum FA, de Prat-Gay G.

Biochemistry. 2003 May 27;42(20):6218-27.

PMID:12755625

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Antibody response to a viral transcriptional regulator.

Cerutti ML, Centeno JM, de Prat-Gay G, Goldbaum FA.

FEBS Lett. 2003 Jan 16;534(1-3):202-6.

PMID:12527387

---

New approaches to improve a peptide vaccine against porcine Taenia solium cysticercosis.

Sciutto E, Fragoso G, Manoutcharian K, Gevorkian G, Rosas-Salgado G, Hernández-Gonzalez M, Herrera-Estrella L, Cabrera-Ponce J, López-Casillas F, González-Bonilla C, Santiago-Machuca A, Ruíz-Pérez F, Sánchez J, Goldbaum F, Aluja A, Larralde C.

Arch Med Res. 2002 Jul-Aug;33(4):371-8. Review.

PMID:12234527

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A DNA vaccine encoding lumazine synthase from Brucella abortus induces protective immunity in BALB/c mice.

Velikovsky CA, Cassataro J, Giambartolomei GH, Goldbaum FA, Estein S, Bowden RA, Bruno L, Fossati CA, Spitz M.

Infect Immun. 2002 May;70(5):2507-11.

PMID:11953389

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Generation of sequence-specific, high affinity anti-DNA antibodies.

Cerutti ML, Centeno JM, Goldbaum FA, de Prat-Gay G.

J Biol Chem. 2001 Apr 20;276(16):12769-73. Epub 2001 Jan 22.

PMID:11279040

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Distinctive cognate sequence discrimination, bound DNA conformation, and binding modes in the E2 C-terminal domains from prototype human and bovine papillomaviruses.

Ferreiro DU, Lima LM, Nadra AD, Alonso LG, Goldbaum FA, de Prat-Gay G.

Biochemistry. 2000 Nov 28;39(47):14692-701.

PMID:11087426

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Three-dimensional structure of the Fab from a human IgM cold agglutinin.

Cauerhff A, Braden BC, Carvalho JG, Aparicio R, Polikarpov I, Leoni J, Goldbaum FA.

J Immunol. 2000 Dec 1;165(11):6422-8.

PMID:11086081

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X-ray crystal structure of an anti-Buckminsterfullerene antibody fab fragment: biomolecular recognition of C(60).

Braden BC, Goldbaum FA, Chen BX, Kirschner AN, Wilson SR, Erlanger BF.

Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12193-7.

PMID:11035793

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Structural, functional and immunological studies on a polymeric bacterial protein.

Baldi PC, Velikovsky CA, Braden BC, Giambartolomei GH, Fossati CA, Goldbaum FA.

Braz J Med Biol Res. 2000 Jul;33(7):741-7.

PMID:10881048

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Divergence in macromolecular assembly: X-ray crystallographic structure analysis of lumazine synthase from Brucella abortus.

Braden BC, Velikovsky CA, Cauerhff AA, Polikarpov I, Goldbaum FA.

J Mol Biol. 2000 Apr 14;297(5):1031-6.

PMID:10764570

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1999-1991

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[Determination of antiprotein antibodies for the diagnosis of brucellosis in animals].

Baldi PC, Goldbaum FA, Velikovsky CA, Wallach JC, Fossati CA.

Rev Argent Microbiol. 1999;31 Suppl 1:49-51. Review. Spanish. No abstract available.

PMID:10509413

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[Diagnosis and progress analysis of human brucellosis via new serological methods].

Wallach JC, Baldi PC, Goldbaum FA, Velikovsky CA, Fossati CA.

Rev Argent Microbiol. 1999;31 Suppl 1:46-8. Review. Spanish. No abstract available.

PMID:10509412

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The 18-kDa cytoplasmic protein of Brucella species --an antigen useful for diagnosis--is a lumazine synthase.

Goldbaum FA, Velikovsky CA, Baldi PC, Mörtl S, Bacher A, Fossati CA.

J Med Microbiol. 1999 Sep;48(9):833-9.

PMID:10482294

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Lack of significant differences in association rates and affinities of antibodies from short-term and long-term responses to hen egg lysozyme.

Goldbaum FA, Cauerhff A, Velikovsky CA, Llera AS, Riottot MM, Poljak RJ.

J Immunol. 1999 May 15;162(10):6040-5.

PMID:10229844

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Crystallization and preliminary x-ray diffraction analysis of the lumazine synthase from Brucella abortus.

Goldbaum FA, Polikarpov I, Cauerhff AA, Velikovsky CA, Braden BC, Poljak RJ.

J Struct Biol. 1998 Oct;123(2):175-8.

PMID:9843672

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Characterization of anti-anti-idiotypic antibodies that bind antigen and an anti-idiotype.

Goldbaum FA, Velikovsky CA, Dall'Acqua W, Fossati CA, Fields BA, Braden BC, Poljak RJ, Mariuzza RA.

Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8697-701.

PMID:9238040

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Hydrogen bonding and solvent structure in an antigen-antibody interface. Crystal structures and thermodynamic characterization of three Fv mutants complexed with lysozyme.

Fields BA, Goldbaum FA, Dall'Acqua W, Malchiodi EL, Cauerhff A, Schwarz FP, Ysern X, Poljak RJ, Mariuzza RA.

Biochemistry. 1996 Dec 3;35(48):15494-503.

PMID:8952503

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Crystal structure of an Fv-Fv idiotope-anti-idiotope complex at 1.9 A resolution.

Braden BC, Fields BA, Ysern X, Dall'Acqua W, Goldbaum FA, Poljak RJ, Mariuzza RA.

J Mol Biol. 1996 Nov 22;264(1):137-51.

PMID:8950273

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Humoral immune response against lipopolysaccharide and cytoplasmic proteins of Brucella abortus in cattle vaccinated with B. abortus S19 or experimentally infected with Yersinia enterocolitica serotype 0:9.

Baldi PC, Giambartolomei GH, Goldbaum FA, Abdón LF, Velikovsky CA, Kittelberger R, Fossati CA.

Clin Diagn Lab Immunol. 1996 Jul;3(4):472-6.

PMID:8807216

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Crystal structure of the complex of the variable domain of antibody D1.3 and turkey egg white lysozyme: a novel conformational change in antibody CDR-L3 selects for antigen.

Braden BC, Fields BA, Ysern X, Goldbaum FA, Dall'Acqua W, Schwarz FP, Poljak RJ, Mariuzza RA.

J Mol Biol. 1996 Apr 19;257(5):889-94.

PMID:8632472

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The effect of water activity on the association constant and the enthalpy of reaction between lysozyme and the specific antibodies D1.3 and D44.1.

Goldbaum FA, Schwarz FP, Eisenstein E, Cauerhff A, Mariuzza RA, Poljak RJ.

J Mol Recognit. 1996 Jan-Feb;9(1):6-12.

PMID:8723314

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Structure and thermodynamics of antigen recognition by antibodies.

Braden BC, Cauerhff A, Dall'Acqua W, Fields BA, Goldbaum FA, Malchiodi EL, Mariuzza RA, Poljak RJ, Schwarz FP, Ysern X, et al.

Ann N Y Acad Sci. 1995 Sep 29;764:315-27. No abstract available.

PMID:7486542

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Molecular basis of antigen mimicry by an anti-idiotope.

Fields BA, Goldbaum FA, Ysern X, Poljak RJ, Mariuzza RA.

Nature. 1995 Apr 20;374(6524):739-42.

PMID:7536303

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Thermodynamics of antigen-antibody binding using specific anti-lysozyme antibodies.

Schwarz FP, Tello D, Goldbaum FA, Mariuzza RA, Poljak RJ.

Eur J Biochem. 1995 Mar 1;228(2):388-94.

PMID:7705353

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Protein motion and lock and key complementarity in antigen-antibody reactions.

Braden BC, Dall'Acqua W, Eisenstein E, Fields BA, Goldbaum FA, Malchiodi EL, Mariuzza RA, Schwarz FP, Ysern X, Poljak RJ.

Pharm Acta Helv. 1995 Mar;69(4):225-30. Review.

PMID:7651966

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Crystallization and preliminary X-ray diffraction study of an idiotope-anti-idiotope Fv-Fv complex.

Goldbaum FA, Fields BA, Cauerhff A, Ysern X, Houdusse A, Eisele JL, Poljak RJ, Mariuzza RA.

J Mol Biol. 1994 Sep 2;241(5):739-43.

PMID:8071997

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Solvent rearrangement in an antigen-antibody interface introduced by site-directed mutagenesis of the antibody combining site.

Ysern X, Fields BA, Bhat TN, Goldbaum FA, Dall'Acqua W, Schwarz FP, Poljak RJ, Mariuzza RA.

J Mol Biol. 1994 May 13;238(4):496-500.

PMID:8176740

---

Structural and physicochemical analysis of the reaction between the anti-lysozyme antibody D1.3 and the anti-idiotopic antibodies E225 and E5.2.

Tello D, Eisenstein E, Schwarz FP, Goldbaum FA, Fields BA, Mariuzza RA, Poljak RJ.

J Mol Recognit. 1994 Mar;7(1):57-62.

PMID:7986568

---

Removal of LPS from a Brucella cytoplasmic fraction by affinity chromatography with an anti-LPS monoclonal antibody as immunosorbent.

Goldbaum FA, Rubbi CP, Fossati CA.

J Med Microbiol. 1994 Mar;40(3):174-8.

PMID:7509415

---

Urban outbreak of a Brucella melitensis infection in an Argentine family: clinical and diagnostic aspects.

Wallach JC, Miguel SE, Baldi PC, Guarnera E, Goldbaum FA, Fossati CA.

FEMS Immunol Med Microbiol. 1994 Jan;8(1):49-56.

PMID:8156050

---

Three-dimensional structure and thermodynamics of antigen binding by anti-lysozyme antibodies.

Tello D, Goldbaum FA, Mariuzza RA, Ysern X, Schwarz FP, Poljak RJ.

Biochem Soc Trans. 1993 Nov;21(4):943-6. No abstract available.

PMID:8132099

---

Characterization of an 18-kilodalton Brucella cytoplasmic protein which appears to be a serological marker of active infection of both human and bovine brucellosis.

Goldbaum FA, Leoni J, Wallach JC, Fossati CA.

J Clin Microbiol. 1993 Aug;31(8):2141-5.

PMID:8370742

---

Differentiation between active and inactive human brucellosis by measuring antiprotein humoral immune responses.

Goldbaum FA, Rubbi CP, Wallach JC, Miguel SE, Baldi PC, Fossati CA.

J Clin Microbiol. 1992 Mar;30(3):604-7.

PMID:1551977

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Human brucellosis: immunoblotting analysis of three Brucella abortus antigenic fractions allows the detection of components of diagnostic importance.

Goldbaum FA, Morelli L, Wallach J, Rubbi CP, Fossati CA.

Medicina (B Aires). 1991;51(3):227-32.

PMID:1726568

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