Structural highlights
4jna is a 4 chain structure with sequence from "chromobacterium_janthinum"_(zopf)_ford_1927 "chromobacterium janthinum" (zopf) ford 1927. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , |
| NonStd Res: | , , , |
| Related: | 4jn9 |
| Gene: | depH ("Chromobacterium janthinum" (Zopf) Ford 1927) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Publication Abstract from PubMed
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 A and 2.00 A, 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.
The structural basis of an NADP(+)-independent dithiol oxidase in FK228 biosynthesis.,Li J, Wang C, Zhang ZM, Cheng YQ, Zhou J Sci Rep. 2014 Feb 20;4:4145. doi: 10.1038/srep04145. PMID:24553401[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Li J, Wang C, Zhang ZM, Cheng YQ, Zhou J. The structural basis of an NADP(+)-independent dithiol oxidase in FK228 biosynthesis. Sci Rep. 2014 Feb 20;4:4145. doi: 10.1038/srep04145. PMID:24553401 doi:http://dx.doi.org/10.1038/srep04145
