View source for 9hqb


==1-Epi-Cubenol Synthase from Nonomuraea coxensis (NcECS) in complex with 2,3-DHFPP==
<StructureSection load='9hqb' size='340' side='right'caption='[[9hqb]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9hqb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Nonomuraea Nonomuraea]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9HQB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9HQB 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]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3E9:(3S,6E)-3,7,11-TRIMETHYLDODECA-6,10-DIEN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>3E9</scene>, <scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=9hqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9hqb OCA], [https://pdbe.org/9hqb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9hqb RCSB], [https://www.ebi.ac.uk/pdbsum/9hqb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9hqb ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Terpene synthases orchestrate complex cyclization cascades that transform simple polyisoprenoid precursors into structurally diverse natural products, often with exquisite stereochemical control. Here we combine high-resolution X-ray crystallography, site-directed mutagenesis, and QM/MM calculations to dissect the catalytic mechanisms of two bacterial sesquiterpene synthases for T-muurolol (TmS) and 1-epi-cubenol (NcECS). The structures reveal a dynamic transition between open and closed states, controlled by a trinuclear magnesium cluster that mediates substrate binding, carbocation formation, and intramolecular pyrophosphate transfer to generate (R)-nerolidyl pyrophosphate, the precursor to Z-configured products. Using synthetic dihydro-surrogates, we identify a counterclockwise substrate orientation, not previously observed in terpene synthases, and visualize a series of trapped hydrocarbons that resemble several of the proposed cationic intermediates along the cyclization cascade. Complementary quantum chemical calculations support their observed geometries and indicate that the active site can transiently accommodate these intermediate analogs, offering a structural basis for understanding how sesquiterpene synthases guide complex carbocationic pathways.

Structural Mimics of Hydrocarbon Intermediates Reveal Counterclockwise Cyclization Pathways in the Sesquiterpene Synthases TmS and NcECS.,Groll M, Li H, Troycke P, Kaila VRI, Dickschat JS J Am Chem Soc. 2025 Dec 10. doi: 10.1021/jacs.5c17732. PMID:41372098<ref>PMID:41372098</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9hqb" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Nonomuraea]]
[[Category: Dickschat JS]]
[[Category: Groll M]]
[[Category: Li H]]
[[Category: Troycke P]]