A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity.
Nat Commun
; 8: 14397, 2017 02 07.
Article
en En
| MEDLINE
| ID: mdl-28169272
ABSTRACT
Biliverdin reductase catalyses the last step in haem degradation and produces the major lipophilic antioxidant bilirubin via reduction of biliverdin, using NAD(P)H as a cofactor. Despite the importance of biliverdin reductase in maintaining the redox balance, the molecular details of the reaction it catalyses remain unknown. Here we present the crystal structure of biliverdin reductase in complex with biliverdin and NADP+. Unexpectedly, two biliverdin molecules, which we designated the proximal and distal biliverdins, bind with stacked geometry in the active site. The nicotinamide ring of the NADP+ is located close to the reaction site on the proximal biliverdin, supporting that the hydride directly attacks this position of the proximal biliverdin. The results of mutagenesis studies suggest that a conserved Arg185 is essential for the catalysis. The distal biliverdin probably acts as a conduit to deliver the proton from Arg185 to the proximal biliverdin, thus yielding bilirubin.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Biliverdina
/
Cianobacterias
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Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH
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NADP
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón