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| | <StructureSection load='5f5l' size='340' side='right'caption='[[5f5l]], [[Resolution|resolution]] 1.68Å' scene=''> | | <StructureSection load='5f5l' size='340' side='right'caption='[[5f5l]], [[Resolution|resolution]] 1.68Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5f5l]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Micromonospora_sp._tp-a0468 Micromonospora sp. tp-a0468]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F5L OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5F5L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5f5l]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Micromonospora_sp._TP-A0468 Micromonospora sp. TP-A0468]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F5L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F5L FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.68Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5f5n|5f5n]]</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=5f5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f5l OCA], [https://pdbe.org/5f5l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f5l RCSB], [https://www.ebi.ac.uk/pdbsum/5f5l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f5l ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5f5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f5l OCA], [http://pdbe.org/5f5l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f5l RCSB], [http://www.ebi.ac.uk/pdbsum/5f5l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f5l ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A023GUL3_9ACTN A0A023GUL3_9ACTN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Micromonospora sp. tp-a0468]] | + | [[Category: Micromonospora sp. TP-A0468]] |
| - | [[Category: Gong, Y]] | + | [[Category: Gong Y]] |
| - | [[Category: Pan, L]] | + | [[Category: Pan L]] |
| - | [[Category: Dearomatization]]
| + | |
| - | [[Category: Kosinostatin]]
| + | |
| - | [[Category: Monooxygenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
A0A023GUL3_9ACTN
Publication Abstract from PubMed
Ranking among the most effective anticancer drugs, anthracyclines represent an important family of aromatic polyketides generated by type II polyketide synthases (PKSs). After formation of polyketide cores, the post-PKS tailoring modifications endow the scaffold with various structural diversities and biological activities. Here we demonstrate an unprecedented four-enzyme-participated hydroxyl regioisomerization process involved in the biosynthesis of kosinostatin. First, KstA15 and KstA16 function together to catalyze a cryptic hydroxylation of the 4-hydroxyl-anthraquinone core, yielding a 1,4-dihydroxyl product, which undergoes a chemically challenging asymmetric reduction-dearomatization subsequently acted by KstA11; then, KstA10 catalyzes a region-specific reduction concomitant with dehydration to afford the 1-hydroxyl anthraquinone. Remarkably, the shunt product identifications of both hydroxylation and reduction-dehydration reactions, the crystal structure of KstA11 with bound substrate and cofactor, and isotope incorporation experiments reveal mechanistic insights into the redox dearomatization and rearomatization steps. These findings provide a distinguished tailoring paradigm for type II PKS engineering.
Hydroxyl regioisomerization of anthracycline catalyzed by a four-enzyme cascade.,Zhang Z, Gong YK, Zhou Q, Hu Y, Ma HM, Chen YS, Igarashi Y, Pan L, Tang GL Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1554-1559. doi:, 10.1073/pnas.1610097114. Epub 2017 Jan 30. PMID:28137838[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang Z, Gong YK, Zhou Q, Hu Y, Ma HM, Chen YS, Igarashi Y, Pan L, Tang GL. Hydroxyl regioisomerization of anthracycline catalyzed by a four-enzyme cascade. Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1554-1559. doi:, 10.1073/pnas.1610097114. Epub 2017 Jan 30. PMID:28137838 doi:http://dx.doi.org/10.1073/pnas.1610097114
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