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The structural basis of an NADP(+)-independent dithiol oxidase in FK228 biosynthesis
Alternative TitleThe structural basis of an NADP(+)-independent dithiol oxidase in FK228 biosynthesis
LI JIE; WANG CHENG; ZHANG ZHIMIN; CHENG YIQIANG; Zhou JH(周佳海)
2014
Source PublicationSci Rep
Volume4Pages:4145
AbstractThe disulfide bond is unusual in natural products and critical for thermal stability, cell permeability and bioactivity. DepH from Chromobacterium violaceum No. 968 is an FAD-dependent enzyme responsible for catalyzing the disulfide bond formation of FK228, an anticancer prodrug approved for the treatment of cutaneous T-cell lymphoma. Here we report the crystal structures of DepH and DepH complexed with a substrate analogue S, S'-dimethyl FK228 at 1.82 angstrom and 2.00 angstrom, respectively. Structural and biochemical analyses revealed that DepH, in contrast to the well characterized low molecular weight thioredoxin reductases (LMW TrxRs), is an NADP(+)-independent dithiol oxidase. DepH not only lacks a conserved GGGDXAXE motif necessary for NADP(+) binding in the canonical LMW TrxRs, but also contains a 11-residue sequence which physically impedes the binding of NADP(+). These observations explain the difference between NADP(+)-independent small molecule dithiol oxidases and NADP(+)-dependent thioredoxin reductases and provide insights for understanding the catalytic mechanism of dithiol oxidases involved in natural product biosynthesis.
Subject Area生命有机化学
DOI10.1038/srep04145
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Indexed BySCI
Language英语
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Cited Times:7[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.sioc.ac.cn/handle/331003/38932
Collection生命有机化学国家重点实验室
Affiliation中科院上海有机化学研究所
Recommended Citation
GB/T 7714
LI JIE,WANG CHENG,ZHANG ZHIMIN,et al. The structural basis of an NADP(+)-independent dithiol oxidase in FK228 biosynthesis[J]. Sci Rep,2014,4:4145.
APA LI JIE,WANG CHENG,ZHANG ZHIMIN,CHENG YIQIANG,&周佳海.(2014).The structural basis of an NADP(+)-independent dithiol oxidase in FK228 biosynthesis.Sci Rep,4,4145.
MLA LI JIE,et al."The structural basis of an NADP(+)-independent dithiol oxidase in FK228 biosynthesis".Sci Rep 4(2014):4145.
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