9kpp: Difference between revisions
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==Crystal structure of FrazP2== | |||
<StructureSection load='9kpp' size='340' side='right'caption='[[9kpp]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9kpp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Actinomadura_sp. Actinomadura sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9KPP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9KPP FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=9kpp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9kpp OCA], [https://pdbe.org/9kpp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9kpp RCSB], [https://www.ebi.ac.uk/pdbsum/9kpp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9kpp ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A5J6UCU5_9ACTN A0A5J6UCU5_9ACTN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Forazoline A, produced by the marine actinomycete Actinomadura sp. WMMB-499, is a unique PK/NRP hybrid macrolactone with promising antifungal in vivo efficacy through a previously unreported mechanism. Although a PKS/NRPS gene cluster was identified as a candidate for forazoline production, the precise biosynthetic pathway and the functions of the tailoring enzymes remain unclear. In this work, the functions of three cytochrome P450 mono-oxygenases (FrazP1P2P3) were characterized. Notably, FrazP2 was found to mediate cyclohexane ring formation from an 1,3,6-triene precursor during forazoline A biosynthesis, as confirmed by genetic and biochemical analysis. To gain structural and mechanistic insight into the activity of FrazP2, the crystal structure of a FrazP2-substrate complex has been solved at 2.3 A resolution. The molecular dynamics simulations and DFT calculations revealed an unprecedented enzyme-catalyzed oxidative cyclization reaction by FrazP2. These findings expand our understanding of the catalytic diversity of cytochrome P450s, contributing to the diversification of natural products and enabling the creation of unnatural derivatives with increased antifungal potency. | |||
Cytochrome P450 Mediated Cyclohexane Ring Formation in Forazoline Biosynthesis.,Chen X, Zhang Y, Li S, Liao W, Tao W, Deng Z, Bugni TS, Su H, Zhang F Angew Chem Int Ed Engl. 2025 May 6:e202504925. doi: 10.1002/anie.202504925. PMID:40329414<ref>PMID:40329414</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Chen | <div class="pdbe-citations 9kpp" style="background-color:#fffaf0;"></div> | ||
[[Category: Zhang | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Actinomadura sp]] | |||
[[Category: Large Structures]] | |||
[[Category: Chen XR]] | |||
[[Category: Zhang F]] | |||
