A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes
Autor(a) principal: | |
---|---|
Data de Publicação: | 1996 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/143739 |
Resumo: | The crystal structure of the xanthine oxidase-related molybdenum-iron protein aldehyde oxidoreductase from the sulfate reducing anaerobic Gram- negative bacterium Desulfovibrio gigas (Mop) was analyzed in its desulfo-, sulfo-, oxidized, reduced, and alcohol-bound forms at 1.8-Å resolution. In the sulfo-form the molybdenum molybdopterin cytosine dinucleotide cofactor has a dithiolenebound fac-[Mo, =O, =S, ···(OH2)] substructure. Bound inhibitory isopropanol in the inner compartment of the substrate binding tunnel is a model for the Michaelis complex of the reaction with aldehydes (H-C=O, -R). The reaction is proposed to proceed by transfer of the molybdenum-bound water molecule as OH- after proton transfer to Glu-869 to the carbonyl carbon of the substrate in concert with hydride transfer to the sulfido group to generate [MoIV, =O, -SH, ···(O-C=O, -R)). Dissociation of the carboxylic acid product may be facilitated by transient binding of Glu- 869 to the molybdenum. The metal-bound water is replenished from a chain of internal water molecules. A second alcohol binding site in the spacious outer compartment may cause the strong substrate inhibition observed. This compartment is the putative binding site of large inhibitors of xanthine oxidase. |
id |
RCAP_a20be4a47e1294fd88ed6d81e1fda36b |
---|---|
oai_identifier_str |
oai:run.unl.pt:10362/143739 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymesGeneralThe crystal structure of the xanthine oxidase-related molybdenum-iron protein aldehyde oxidoreductase from the sulfate reducing anaerobic Gram- negative bacterium Desulfovibrio gigas (Mop) was analyzed in its desulfo-, sulfo-, oxidized, reduced, and alcohol-bound forms at 1.8-Å resolution. In the sulfo-form the molybdenum molybdopterin cytosine dinucleotide cofactor has a dithiolenebound fac-[Mo, =O, =S, ···(OH2)] substructure. Bound inhibitory isopropanol in the inner compartment of the substrate binding tunnel is a model for the Michaelis complex of the reaction with aldehydes (H-C=O, -R). The reaction is proposed to proceed by transfer of the molybdenum-bound water molecule as OH- after proton transfer to Glu-869 to the carbonyl carbon of the substrate in concert with hydride transfer to the sulfido group to generate [MoIV, =O, -SH, ···(O-C=O, -R)). Dissociation of the carboxylic acid product may be facilitated by transient binding of Glu- 869 to the molybdenum. The metal-bound water is replenished from a chain of internal water molecules. A second alcohol binding site in the spacious outer compartment may cause the strong substrate inhibition observed. This compartment is the putative binding site of large inhibitors of xanthine oxidase.DQ - Departamento de QuímicaProgramme in Translational Medicine (iNOVA4Health)Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNHuber, RobertHof, PeterDuarte, Rui O.Moura, Jose J. G.Moura, IsabelLiu, Ming YihLeGall, JeanHille, RussArcher, MargaridaRomão, Maria J.2022-09-14T22:28:06Z1996-08-201996-08-20T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article6application/pdfhttp://hdl.handle.net/10362/143739eng0027-8424PURE: 46539931https://doi.org/10.1073/pnas.93.17.8846info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:22:25Zoai:run.unl.pt:10362/143739Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:51:07.032051Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes |
title |
A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes |
spellingShingle |
A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes Huber, Robert General |
title_short |
A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes |
title_full |
A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes |
title_fullStr |
A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes |
title_full_unstemmed |
A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes |
title_sort |
A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes |
author |
Huber, Robert |
author_facet |
Huber, Robert Hof, Peter Duarte, Rui O. Moura, Jose J. G. Moura, Isabel Liu, Ming Yih LeGall, Jean Hille, Russ Archer, Margarida Romão, Maria J. |
author_role |
author |
author2 |
Hof, Peter Duarte, Rui O. Moura, Jose J. G. Moura, Isabel Liu, Ming Yih LeGall, Jean Hille, Russ Archer, Margarida Romão, Maria J. |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
DQ - Departamento de Química Programme in Translational Medicine (iNOVA4Health) Instituto de Tecnologia Química e Biológica António Xavier (ITQB) RUN |
dc.contributor.author.fl_str_mv |
Huber, Robert Hof, Peter Duarte, Rui O. Moura, Jose J. G. Moura, Isabel Liu, Ming Yih LeGall, Jean Hille, Russ Archer, Margarida Romão, Maria J. |
dc.subject.por.fl_str_mv |
General |
topic |
General |
description |
The crystal structure of the xanthine oxidase-related molybdenum-iron protein aldehyde oxidoreductase from the sulfate reducing anaerobic Gram- negative bacterium Desulfovibrio gigas (Mop) was analyzed in its desulfo-, sulfo-, oxidized, reduced, and alcohol-bound forms at 1.8-Å resolution. In the sulfo-form the molybdenum molybdopterin cytosine dinucleotide cofactor has a dithiolenebound fac-[Mo, =O, =S, ···(OH2)] substructure. Bound inhibitory isopropanol in the inner compartment of the substrate binding tunnel is a model for the Michaelis complex of the reaction with aldehydes (H-C=O, -R). The reaction is proposed to proceed by transfer of the molybdenum-bound water molecule as OH- after proton transfer to Glu-869 to the carbonyl carbon of the substrate in concert with hydride transfer to the sulfido group to generate [MoIV, =O, -SH, ···(O-C=O, -R)). Dissociation of the carboxylic acid product may be facilitated by transient binding of Glu- 869 to the molybdenum. The metal-bound water is replenished from a chain of internal water molecules. A second alcohol binding site in the spacious outer compartment may cause the strong substrate inhibition observed. This compartment is the putative binding site of large inhibitors of xanthine oxidase. |
publishDate |
1996 |
dc.date.none.fl_str_mv |
1996-08-20 1996-08-20T00:00:00Z 2022-09-14T22:28:06Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/143739 |
url |
http://hdl.handle.net/10362/143739 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0027-8424 PURE: 46539931 https://doi.org/10.1073/pnas.93.17.8846 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
6 application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799138106190856192 |