Artículo
Human Heme Oxygenase Oxidation of 5- and 15-Phenylhemes
Wang, Jingling; Niemevz, Fernando; Lad, Latesh; Huang, Liusheng; Alvarez, Diego Ezequiel
; Buldain, Graciela Yolanda
; Poulos, Thomas L.; Ortiz de Montellano, Paul R.
Fecha de publicación:
10/2004
Editorial:
American Society for Biochemistry and Molecular Biology
Revista:
Journal of Biological Chemistry (online)
ISSN:
0021-9258
e-ISSN:
1083-351X
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Human heme oxygenase-1 (hHO-1) catalyzes the O2- dependent oxidation of heme to biliverdin, CO, and free iron. Previous work indicated that electrophilic addition of the terminal oxygen of the ferric hydroperoxo complex to the -meso-carbon gives 5-hydroxyheme. Earlier efforts to block this reaction with a 5-methyl substituent failed, as the reaction still gave biliverdin IX . Surprisingly, a 15-methyl substituent caused exclusive cleavage at the -meso- rather than at the normal, unsubstituted -meso-carbon. No CO was formed in these reactions, but the fragment cleaved from the porphyrin eluded identification. We report here that hHO-1 cleaves 5-phenylheme to biliverdin IX and oxidizes 15- phenylheme at the -meso position to give 10-phenylbiliverdin IX . The fragment extruded in the oxidation of 5-phenylheme is benzoic acid, one oxygen of which comes from O2 and the other from water. The 2.29- and 2.11-Å crystal structures of the hHO-1 complexes with 1- and 15-phenylheme, respectively, show clear electron density for both the 5- and 15-phenyl rings in both molecules of the asymmetric unit. The overall structure of 15-phenylheme-hHO-1 is similar to that of heme-hHO-1 except for small changes in distal residues 141–150 and in the proximal Lys18 and Lys22. In the 5-phenylhemehHO-1 structure, the phenyl-substituted heme occupies the same position as heme in the heme-HO-1 complex but the 5-phenyl substituent disrupts the rigid hydrophobic wall of residues Met34, Phe214, and residues 26–42 near the -meso carbon. The results provide independent support for an electrophilic oxidation mechanism and support a role for stereochemical control of the reaction regiospecificity.
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IIB-INTECH)
Articulos de INST.DE INVEST.BIOTECNOLOGICAS - INSTITUTO TECNOLOGICO CHASCOMUS
Articulos de INST.DE INVEST.BIOTECNOLOGICAS - INSTITUTO TECNOLOGICO CHASCOMUS
Articulos(IIBBA)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Wang, Jingling; Niemevz, Fernando; Lad, Latesh; Huang, Liusheng; Alvarez, Diego Ezequiel; et al.; Human Heme Oxygenase Oxidation of 5- and 15-Phenylhemes; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 279; 41; 10-2004; 42593-42604
Compartir
Altmétricas