Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/14405
Title: Crystal structure of bacterial morphinone reductase and properties of the C191A mutant enzyme.
Authors: Barna, T
Messiha, HL
Petosa, C
Bruce, NC
Scrutton, NS
Moody, PC
First Published: 23-Aug-2002
Citation: J BIOL CHEM, 2002, 277 (34), pp. 30976-30983
Abstract: The crystal structure of the NADH-dependent bacterial flavoenzyme morphinone reductase (MR) has been determined at 2.2-A resolution in complex with the oxidizing substrate codeinone. The structure reveals a dimeric enzyme comprising two 8-fold beta/alpha barrel domains, each bound to FMN, and a subunit folding topology and mode of flavin-binding similar to that found in Old Yellow Enzyme (OYE) and pentaerythritol tetranitrate (PETN) reductase. The subunit interface of MR is formed by interactions from an N-terminal beta strand and helices 2 and 8 of the barrel domain and is different to that seen in OYE. The active site structures of MR, OYE, and PETN reductase are highly conserved reflecting the ability of these enzymes to catalyze "generic" reactions such as the reduction of 2-cyclohexenone. A region of polypeptide presumed to define the reducing coenzyme specificity is identified by comparison of the MR structure (NADH-dependent) with that of PETN reductase (NADPH-dependent). The active site acid identified in OYE (Tyr-196) and conserved in PETN reductase (Tyr-186) is replaced by Cys-191 in MR. Mutagenesis studies have established that Cys-191 does not act as a crucial acid in the mechanism of reduction of the olefinic bond found in 2-cyclohexenone and codeinone.
DOI Link: 10.1074/jbc.M202846200
ISSN: 0021-9258
Links: http://hdl.handle.net/2381/14405
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Biochemistry

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