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| == Function == | | == Function == |
| [https://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> | | [https://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> |
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| == Publication Abstract from PubMed ==
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| The diterpene cyclase CotB2 catalyzes the cyclization of geranylgeranyl diphosphate (GGPP) to the tricyclic cyclooctat-9-en-7-ol, which is characterized by a 5-8-5-fused ring skeleton. We have previously proposed a cyclization cascade involving a unique carbon-carbon bond rearrangement combined with multiple hydride shifts, all occurring at a single active site. Here, we report the first high-resolution X-ray crystal structure of CotB2 with bound substrate analog geranylgeranyl thiodiphosphate (GGSPP). In the GGSPP-bound form, GGSPP folds into a unique S-shaped conformation that probably reflects the substrate-bound state prior to ionization of the substrate GGPP. The folded framework of GGSPP is surrounded by hydrophobic residues and several aromatic and asparagine residues that are well-positioned to stabilize a series of reactive carbocation intermediates through a combination of cation-pi and dipole charge interactions. The combined crystal structures and mutagenesis-based biochemical assays provide a structural basis for exquisite control of ring formation and stereochemistry during CotB2 catalysis.
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| Structural Insights into the CotB2-Catalyzed Cyclization of Geranylgeranyl Diphosphate to the Diterpene Cyclooctat-9-en-7-ol.,Tomita T, Kim SY, Teramoto K, Meguro A, Ozaki T, Yoshida A, Motoyoshi Y, Mori N, Ishigami K, Watanabe H, Nishiyama M, Kuzuyama T ACS Chem Biol. 2017 Jun 16;12(6):1621-1628. doi: 10.1021/acschembio.7b00154. Epub, 2017 May 2. PMID:28463490<ref>PMID:28463490</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| == References == | | == References == |
| <references/> | | <references/> |
