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| | ==Crystal structure of the DepH complex with dimethyl-FK228== | | ==Crystal structure of the DepH complex with dimethyl-FK228== |
| - | <StructureSection load='4jna' size='340' side='right' caption='[[4jna]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4jna' size='340' side='right'caption='[[4jna]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jna]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"chromobacterium_janthinum"_(zopf)_ford_1927 "chromobacterium janthinum" (zopf) ford 1927]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JNA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JNA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jna]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Chromobacterium_violaceum Chromobacterium violaceum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JNA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JNA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=060:S-METHYL-D-CYSTEINE'>060</scene>, <scene name='pdbligand=1KC:(3S)-7-METHYLSULFANYL-3-OXIDANYL-HEPT-4-ENOIC+ACID'>1KC</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DBU:(2Z)-2-AMINOBUT-2-ENOIC+ACID'>DBU</scene>, <scene name='pdbligand=DVA:D-VALINE'>DVA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=060:S-METHYL-D-CYSTEINE'>060</scene>, <scene name='pdbligand=1KC:(3S)-7-METHYLSULFANYL-3-OXIDANYL-HEPT-4-ENOIC+ACID'>1KC</scene>, <scene name='pdbligand=DBU:(2Z)-2-AMINOBUT-2-ENOIC+ACID'>DBU</scene>, <scene name='pdbligand=DVA:D-VALINE'>DVA</scene></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4jna FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jna OCA], [https://pdbe.org/4jna PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jna RCSB], [https://www.ebi.ac.uk/pdbsum/4jna PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jna ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jn9|4jn9]]</td></tr> | + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">depH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=536 "Chromobacterium janthinum" (Zopf) Ford 1927])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jna FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jna OCA], [http://pdbe.org/4jna PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jna RCSB], [http://www.ebi.ac.uk/pdbsum/4jna PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jna ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A4ZPY8_CHRVL A4ZPY8_CHRVL] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cheng, E]] | + | [[Category: Chromobacterium violaceum]] |
| - | [[Category: Li, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Wang, C]] | + | [[Category: Cheng E]] |
| - | [[Category: Zhang, Z M]] | + | [[Category: Li J]] |
| - | [[Category: Zhou, J H]]
| + | [[Category: Wang C]] |
| - | [[Category: Depsipeptide]] | + | [[Category: Zhang ZM]] |
| - | [[Category: Disulfide bond formation]] | + | [[Category: Zhou JH]] |
| - | [[Category: Fad-dependent oxidoreductase]] | + | |
| - | [[Category: Fk228]]
| + | |
| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
| + | |
| Structural highlights
4jna is a 4 chain structure with sequence from Chromobacterium violaceum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
A4ZPY8_CHRVL
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
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