View source for 6ggi


==Crystal structure of CotB2 in complex with 2-fluoro-3,7,18-dolabellatriene==
<StructureSection load='6ggi' size='340' side='right' caption='[[6ggi]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ggi]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GGI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GGI FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CCN:ACETONITRILE'>CCN</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EXW:2-fluoro-3,7,18-dolabellatriene'>EXW</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PPV:PYROPHOSPHATE'>PPV</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lyase Lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.3.146 4.2.3.146] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ggi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ggi OCA], [http://pdbe.org/6ggi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ggi RCSB], [http://www.ebi.ac.uk/pdbsum/6ggi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ggi ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/COTB2_STRMJ COTB2_STRMJ]] Catalyzes the cyclization of the linear isoprenoid intermediate geranylgeranyl diphosphate to tricycclic cyclooctat-9-en-7-ol in the cyclooctatin biosynthesis pathway. Cyclooctatin is a potent inhibitor of lysophospholipase.<ref>PMID:19635410</ref> <ref>PMID:24914964</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Terpenes constitute the largest and structurally most diverse natural product family. Most terpenoids exhibit a stereochemically complex macrocyclic core, which is generated by C-C bond forming of aliphatic oligo-prenyl precursors. This reaction is catalysed by terpene synthases (TPSs), which are capable of chaperoning highly reactive carbocation intermediates through an enzyme-specific reaction. Due to the instability of carbocation intermediates, the proteins' structural dynamics and enzyme:substrate interactions during TPS catalysis remain elusive. Here, we present the structure of the diterpene synthase CotB2, in complex with an in crystallo cyclised abrupt reaction product and a substrate-derived diphosphate. We captured additional snapshots of the reaction to gain an overview of CotB2's catalytic mechanism. To enhance insights into catalysis, structural information is augmented with multiscale molecular dynamic simulations. Our data represent fundamental TPS structure dynamics during catalysis, which ultimately enable rational engineering towards tailored terpene macrocycles that are inaccessible by conventional chemical synthesis.

Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis.,Driller R, Janke S, Fuchs M, Warner E, Mhashal AR, Major DT, Christmann M, Bruck T, Loll B Nat Commun. 2018 Sep 28;9(1):3971. doi: 10.1038/s41467-018-06325-8. PMID:30266969<ref>PMID:30266969</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ggi" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Lyase]]
[[Category: Brueck, T]]
[[Category: Christmann, M]]
[[Category: Driller, R]]
[[Category: Fuchs, M]]
[[Category: Janke, S]]
[[Category: Loll, B]]
[[Category: Major, D T]]
[[Category: Mhashal, A R]]
[[Category: Warner, E]]
[[Category: Cyclooctatin]]
[[Category: Terpene synthase]]