Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biochem J ; 443(2): 505-14, 2012 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22300432

RESUMO

The vital signalling molecule NO is produced by mammalian NOS (nitric oxide synthase) enzymes in two steps. L-arginine is converted into NOHA (Nω-hydroxy-L-arginine), which is converted into NO and citrulline. Both steps are thought to proceed via similar mechanisms in which the cofactor BH4 (tetrahydrobiopterin) activates dioxygen at the haem site by electron transfer. The subsequent events are poorly understood due to the lack of stable intermediates. By analogy with cytochrome P450, a haem-iron oxo species may be formed, or direct reaction between a haem-peroxy intermediate and substrate may occur. The two steps may also occur via different mechanisms. In the present paper we analyse the two reaction steps using the G586S mutant of nNOS (neuronal NOS), which introduces an additional hydrogen bond in the active site and provides an additional proton source. In the mutant enzyme, BH4 activates dioxygen as in the wild-type enzyme, but an interesting intermediate haem species is then observed. This may be a stabilized form of the active oxygenating species. The mutant is able to perform step 2 (reaction with NOHA), but not step 1 (with L-arginine) indicating that the extra hydrogen bond enables it to discriminate between the two mono-oxygenation steps. This implies that the two steps follow different chemical mechanisms.


Assuntos
Óxido Nítrico Sintase Tipo I/metabolismo , Cristalografia por Raios X , Ferro/metabolismo , Modelos Moleculares , Mutação , Óxido Nítrico Sintase Tipo I/química , Óxido Nítrico Sintase Tipo I/genética , Oxirredução , Estrutura Terciária de Proteína
2.
Arch Biochem Biophys ; 493(1): 37-52, 2010 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19850002

RESUMO

There are many examples of oxidative enzymes containing both flavin and heme prosthetic groups that carry out the oxidation of their substrate. For the purpose of this article we have chosen five systems. Two of these, the L-lactate dehydrogenase flavocytochrome b(2) and cellobiose dehydrogenase, carry out the catalytic chemistry at the flavin group. In contrast, the remaining three require activation of dioxygen at the heme group in order to accomplish substrate oxidation, these being flavohemoglobin, a nitric oxide dioxygenase, and the mono-oxygenases nitric oxide synthase and flavocytochrome P450 BM3, which functions as a fatty acid hydroxylase. In the light of recent advances we will describe the structures of these enzymes, some of which share significant homology. We will also discuss their diverse and sometimes controversial catalytic mechanisms, and consider electron transfer processes between the redox cofactors in order to provide an overview of this fascinating set of enzymes.


Assuntos
Proteínas de Bactérias/metabolismo , Desidrogenases de Carboidrato/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Flavinas/metabolismo , L-Lactato Desidrogenase (Citocromo)/metabolismo , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Óxido Nítrico Sintase/metabolismo , Proteínas de Bactérias/química , Desidrogenases de Carboidrato/química , Sistema Enzimático do Citocromo P-450/química , L-Lactato Desidrogenase (Citocromo)/química , Modelos Moleculares , NADPH-Ferri-Hemoproteína Redutase/química , Óxido Nítrico Sintase/química , Conformação Proteica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...