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The structural basis of an NADP(+)-independent dithiol oxidase in FK228 biosynthesis
其他题名The 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
发表期刊Sci Rep
卷号4页码:4145
摘要The 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.
学科领域生命有机化学
DOI10.1038/srep04145
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收录类别SCI
语种英语
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文献类型期刊论文
条目标识符http://ir.sioc.ac.cn/handle/331003/38932
专题生命有机化学国家重点实验室
作者单位中科院上海有机化学研究所
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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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