View source for 8kih


==PhmA, a type I diterpene synthase without NST/DTE motif==
<StructureSection load='8kih' size='340' side='right'caption='[[8kih]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8kih]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Phoma Phoma]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8KIH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8KIH 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]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FGG:(2Z,6E,10E)-2-FLUORO-3,7,11,15-TETRAMETHYLHEXADECA-2,6,10,14-TETRAEN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>FGG</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8kih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8kih OCA], [https://pdbe.org/8kih PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8kih RCSB], [https://www.ebi.ac.uk/pdbsum/8kih PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8kih ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Phomactin diterpenoids possess a unique bicyclo[9.3.1]pentadecane skeleton with multiple oxidative modifications, and are good platelet-activating factor (PAF) antagonists that can inhibit PAF-induced platelet aggregation. In this study, we identified the gene cluster (phm) responsible for the biosynthesis of phomactins from a marine fungus, Phoma sp. ATCC 74077. Despite the complexity of their structures, phomactin biosynthesis only requires two enzymes: a type I diterpene cyclase PhmA and a P450 monooxygenase PhmC. PhmA was found to catalyze the formation of the phomactatriene, while PhmC sequentially catalyzes the oxidation of multiple sites, leading to the generation of structurally diverse phomactins. The rearrangement mechanism of the diterpene scaffold was investigated through isotope labeling experiments. Additionally, we obtained the crystal complex of PhmA with its substrate analogue FGGPP and elucidated the novel metal-ion-binding mode and enzymatic mechanism of PhmA through site-directed mutagenesis. This study provides the first insight into the biosynthesis of phomactins, laying the foundation for the efficient production of phomactin natural products using synthetic biology approaches.

Biosynthesis of Phomactin Platelet Activating Factor Antagonist Requires a Two-Enzyme Cascade.,Zhang L, Zhang B, Zhu A, Liu SH, Wu R, Zhang X, Xu Z, Tan RX, Ge HM Angew Chem Int Ed Engl. 2023 Nov 20;62(47):e202312996. doi: , 10.1002/anie.202312996. Epub 2023 Oct 19. PMID:37804495<ref>PMID:37804495</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8kih" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Phoma]]
[[Category: Ge HM]]
[[Category: Zhang B]]
[[Category: Zhang Y]]
[[Category: Zhu A]]