8h4p

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Current revision (05:54, 23 August 2023) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 8h4p is ON HOLD until 2024-10-11
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==class I sesquiterpene synthase==
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<StructureSection load='8h4p' size='340' side='right'caption='[[8h4p]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8h4p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Fusarium_graminearum_PH-1 Fusarium graminearum PH-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8H4P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8H4P FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.47&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTM:N-BENZYL-N,N-DIETHYLETHANAMINIUM'>BTM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PPV:PYROPHOSPHATE'>PPV</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8h4p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8h4p OCA], [https://pdbe.org/8h4p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8h4p RCSB], [https://www.ebi.ac.uk/pdbsum/8h4p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8h4p ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CLM1_GIBZE CLM1_GIBZE] Terpene cyclase involved in the biosynthesis of culmorin, a tricyclic sesquiterpene diol reported to have antifungal activity and some phytotoxicity to wheat coleoptile tissue, contributing to Fusarium head blight disease (PubMed:19880637) (Probable). The terpene cyclase CLM1 is responsible for the cyclization of farnesyl diphosphate into the intermediate longiborneol (PubMed:19880637). Longiborneol is then hydroxylated in a regio- and endo-stereoselective manner at position C-11 by the cytochrome P450 monooxygenase CLM2 to produce culmorin (PubMed:26673640). Additional non-specific oxygenases are also able to hydroxylate longiborneol at other sites than C-11 leading to 3-hydroxylongiborneol, 5-hydroxylongiborneol, 12-hydroxylongiborneol and 15-hydroxylongiborneol (PubMed:26673640). Moreover, another oxygenase capable of installing a C-11 exo-hydroxy group in longiborneol can also yield 11-epi-acetylculmorin (PubMed:26673640). The production of these longiborneol derivatives is dwarfed by the high abundance of culmorin, suggesting that CLM2 displays superior enzymatic activity to the unidentified, possibly promiscuous, additional oxygenases (PubMed:26673640).<ref>PMID:19880637</ref> <ref>PMID:26673640</ref> <ref>PMID:27324634</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The cyclization of farnesyl diphosphate (FPP) into highly strained polycyclic sesquiterpenes is challenging. We here determined the crystal structures of three sesquiterpene synthases (STSs, namely, BcBOT2, DbPROS, and CLM1) catalyzing the biosynthesis of the tricyclic sesquiterpenes presilphiperfolan-8beta-ol (1), Delta(6)-protoilludene (2), and longiborneol (3). All three STS structures contain a substrate mimic, the benzyltriethylammonium cation (BTAC), in their active sites, providing ideal templates for quantum mechanics/molecular mechanics (QM/MM) analyses toward their catalytic mechanisms. The QM/MM-based molecular dynamics (MD) simulations revealed the cascade reactions toward the enzyme products, and different key active site residues that play important roles in stabilizing reactive carbocation intermediates along the three pathways. Site-directed mutagenesis experiments confirmed the roles of these key residues and concomitantly resulted in 17 shunt products (4-20). Isotopic labeling experiments addressed the key hydride and methyl migrations toward the main and several shunt products. These combined methods provided deep insights into the catalytic mechanisms of the three STSs and demonstrated how the chemical space of STSs can rationally be expanded, which may facilitate applications in synthetic biology approaches toward pharmaceutical and perfumery agents.
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Authors: Li, A.N., Lou, T.T., Ma, M.
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Structural Insights into Three Sesquiterpene Synthases for the Biosynthesis of Tricyclic Sesquiterpenes and Chemical Space Expansion by Structure-Based Mutagenesis.,Lou T, Li A, Xu H, Pan J, Xing B, Wu R, Dickschat JS, Yang D, Ma M J Am Chem Soc. 2023 Apr 5. doi: 10.1021/jacs.3c00278. PMID:37018048<ref>PMID:37018048</ref>
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Description: class I sesquiterpene synthase
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Li, A.N]]
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<div class="pdbe-citations 8h4p" style="background-color:#fffaf0;"></div>
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[[Category: Lou, T.T]]
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== References ==
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[[Category: Ma, M]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Fusarium graminearum PH-1]]
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[[Category: Large Structures]]
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[[Category: Li AN]]
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[[Category: Lou TT]]
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[[Category: Ma M]]

Current revision

class I sesquiterpene synthase

PDB ID 8h4p

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