View source for 6wkd


==Crystal structure of pentalenene synthase complexed with 12,13-difluorofarnesyl diphosphate==
<StructureSection load='6wkd' size='340' side='right'caption='[[6wkd]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wkd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp. Streptomyces sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WKD 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FDF:(2E,6E)-12-FLUORO-11-(FLUOROMETHYL)-3,7-DIMETHYLDODECA-2,6,10-TRIEN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>FDF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6wkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wkd OCA], [https://pdbe.org/6wkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wkd RCSB], [https://www.ebi.ac.uk/pdbsum/6wkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wkd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PENA_STREX PENA_STREX] Catalyzes the cyclization of farnesyl diphosphate (FPP) to the tricyclic sesquiterpene pentalenene, which is the hydrocarbon precursor of the pentalenolactone family of antibiotics produced by a variety of Streptomyces species.<ref>PMID:8180213</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Most terpene synthase reactions follow Markovnikov rules for formation of high-energy carbenium ion intermediates. However, there are notable exceptions. For example, pentalenene synthase (PS) undergoes an initial anti-Markovnikov cyclization reaction followed by a 1,2-hydride shift to form an intermediate humulyl cation with positive charge on the secondary carbon C9 atom of the farnesyl diphosphate substrate. The mechanism by which these enzymes stabilize and guide the regioselectivity of secondary carbocations has not heretofore been elucidated. In an effort to better understand these reactions, we grew crystals of apo-PS, soaked them with the nonreactive substrate analogue 12,13-difluorofarnesyl diphosphate, and determined the X-ray structure of the resulting complex at 2.2 A resolution. The most striking feature of the active site structure is that C9 is perfectly positioned to make a C-H...pi interaction with the side chain benzene ring of residue F76; this would enhance hyperconjugation to stabilize a developing cation at C10 and thus support the anti-Markovnikov regioselectivity of the cyclization. The benzene ring is also positioned to catalyze the migration of H to C10 and stabilize a C9 carbocation. On the opposite face of C9, further cation stabilization is possible via interactions with the main chain carbonyl of I177 and the neighboring intramolecular C6 horizontal lineC7 bond. Mutagenesis experiments also support a role for residue 76 in these interactions, but most interesting is the F76W mutant, whose crystal structure clearly shows C9 and C10 centered above the fused benzene and pyrrole rings of the indole side chain, respectively, such that a carbocation at either position could be stabilized in this complex, and two anti-Markovnikov products, pentalenene and humulene, are formed. Finally, we show that there is a rough correlation (although not absolute) of an aromatic side chain (F or Y) at position 76 in related terpene synthases from Streptomyces that catalyze similar anti-Markovnikov addition reactions.

Mechanism Underlying Anti-Markovnikov Addition in the Reaction of Pentalenene Synthase.,Matos JO, Kumar RP, Ma AC, Patterson M, Krauss IJ, Oprian DD Biochemistry. 2020 Aug 18. doi: 10.1021/acs.biochem.0c00518. PMID:32786410<ref>PMID:32786410</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wkd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces sp]]
[[Category: Matos JO]]
[[Category: Oprian DD]]
[[Category: Prem Kumar R]]