Document Detail

Structural insights into substrate and coenzyme preference by SDR family protein Gox2253 from Gluconobater oxydans.
MedLine Citation:
PMID:  24825769     Owner:  NLM     Status:  Publisher    
Gox2253 from Gluconobacter oxydans belongs to the short-chain dehydrogenases/reductases (SDR) family, and catalyzes the reduction of heptanal, octanal, nonanal and decanal with NADPH. To develop a robust working platform to engineer novel G. oxydans oxidoreductases with designed coenzyme preference, we adopted a structure based rational design strategy using computational predictions that considers the number of hydrogen bonds formed between enzyme and docked coenzyme. We report the crystal structure of Gox2253 at 2.6 Å resolution, ternary models of Gox2253 mutants in complex with NADH/short-chain aldehydes and propose a structural mechanism of substrate selection. Molecular dynamics simulation shows that hydrogen bonds could form between 2'-hydroxyl group in the adenosine moiety of NADH and the side chain of Gox2253 mutant after arginine at position 42 is replaced with tyrosine or lysine. Consistent with the molecular dynamics prediction, Gox2253-R42Y/K mutants can use both NADH and NADPH as a coenzyme. Hence, the strategies here could provide a practical platform to engineer coenzyme selectivity for any given oxidoreductase and could serve as an additional consideration to engineer substrate-binding pockets. © Proteins 2014;. © 2014 Wiley Periodicals, Inc.
Bo Yin; Dongbing Cui; Lujia Zhang; Shuiqin Jiang; Satoru Machida; Y Adam Yuan; Dongzhi Wei
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-5-13
Journal Detail:
Title:  Proteins     Volume:  -     ISSN:  1097-0134     ISO Abbreviation:  Proteins     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-5-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8700181     Medline TA:  Proteins     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Wiley Periodicals, Inc., a Wiley company.
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