View source for 9hr3


==T-Muurolol Synthase from Roseiflexus castenholzii (TmS) in complex with converted 6,7-DHFPP (compound 3+)==
<StructureSection load='9hr3' size='340' side='right'caption='[[9hr3]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9hr3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Roseiflexus_castenholzii Roseiflexus castenholzii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9HR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9HR3 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1IWZ:(1~{Z},3~{E},5~{R},8~{S})-2,8-dimethyl-5-propan-2-yl-cyclodeca-1,3-diene'>A1IWZ</scene>, <scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</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=9hr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9hr3 OCA], [https://pdbe.org/9hr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9hr3 RCSB], [https://www.ebi.ac.uk/pdbsum/9hr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9hr3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TMUUS_ROSCS TMUUS_ROSCS] Catalyzes the conversion of (2E,6E)-farnesyl diphosphate (FPP) into (+)-T-muurolol via a 1,10-cyclization, which requires isomerization of FPP to nerolidyl diphosphate (NPP) and then abstraction of the pyrophosphate from intermediate NPP leading to a (E,Z)-germacradienyl (helminthogermacradienyl) cation.<ref>PMID:23307484</ref> <ref>PMID:27666571</ref> <ref>PMID:27829890</ref> 
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== 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>
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<div class="pdbe-citations 9hr3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Roseiflexus castenholzii]]
[[Category: Dickschat JS]]
[[Category: Groll M]]
[[Category: Li H]]
[[Category: Troycke P]]