5gue

Crystal structure of CotB2 (GGSPP/Mg2+-Bound Form) from Streptomyces melanosporofaciens

spinqualitylabelsall models 5gue, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5gue is a 4 chain structure with sequence from Streptomyces melanosporofaciens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: GGS, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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