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dc.contributor.author
Serer, María Inés
dc.contributor.author
Bonomi, Hernan Ruy
dc.contributor.author
Guimarães, Beatriz G
dc.contributor.author
Rossi, Rolando Carlos
dc.contributor.author
Goldbaum, Fernando Alberto
dc.contributor.author
Klinke, Sebastian
dc.date.available
2016-11-30T20:09:34Z
dc.date.issued
2014-05
dc.identifier.citation
Serer, María Inés; Bonomi, Hernan Ruy; Guimarães, Beatriz G; Rossi, Rolando Carlos; Goldbaum, Fernando Alberto; et al.; Crystallographic and kinetic study of riboflavin synthase from Brucella abortus, a chemotherapeutic target with an enhanced intrinsic flexibility; International Union of Crystallography; Acta Crystallographica Section D-biological Crystallography; 70; 5; 5-2014; 1419-1434
dc.identifier.issn
0907-4449
dc.identifier.uri
http://hdl.handle.net/11336/8538
dc.description.abstract
Riboflavin synthase (RS) catalyzes the last step of riboflavin biosynthesis in microorganisms and plants, which corresponds to the dismutation of two molecules of 6,7-dimethyl-8-ribityllumazine to yield one molecule of riboflavin and one molecule of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione. Owing to the absence of this enzyme in animals and the fact that most pathogenic bacteria show a strict dependence on riboflavin biosynthesis, RS has been proposed as a potential target for antimicrobial drug development. Eubacterial, fungal and plant RSs assemble as homotrimers lacking C3 symmetry. Each monomer can bind two substrate molecules, yet there is only one active site for the whole enzyme, which is located at the interface between two neighbouring chains. This work reports the crystallographic structure of RS from the pathogenic bacterium Brucella abortus (the aetiological agent of the disease brucellosis) in its apo form, in complex with riboflavin and in complex with two different product analogues, being the first time that the structure of an intact RS trimer with bound ligands has been solved. These crystal models support the hypothesis of enhanced flexibility in the particle and also highlight the role of the ligands in assembling the unique active site. Kinetic and binding studies were also performed to complement these findings. The structural and biochemical information generated may be useful for the rational design of novel RS inhibitors with antimicrobial activity.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
International Union of Crystallography
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Enzyme-Ligand Complex
dc.subject
Inhibition by Substrate And Product
dc.subject
6,7-Dimethyl-8-Ribityllumazine
dc.subject
Vitamin B2
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Crystallographic and kinetic study of riboflavin synthase from Brucella abortus, a chemotherapeutic target with an enhanced intrinsic flexibility
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-11-29T12:42:42Z
dc.journal.volume
70
dc.journal.number
5
dc.journal.pagination
1419-1434
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: Serer, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
dc.description.fil
Fil: Bonomi, Hernan Ruy. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
dc.description.fil
Fil: Guimarães, Beatriz G. Soleil Synchrotron; Francia
dc.description.fil
Fil: Rossi, Rolando Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentina
dc.description.fil
Fil: Goldbaum, Fernando Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
dc.description.fil
Fil: Klinke, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
dc.journal.title
Acta Crystallographica Section D-biological Crystallography
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://scripts.iucr.org/cgi-bin/paper?S1399004714005161
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1107/S1399004714005161
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014124/


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