7ao0 | pdb_00007ao0

Crystal structure of CotB2 variant F107A in complex with alendronate

spinqualitylabelsall models 7ao0, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ao0 is a 2 chain structure with sequence from Atcc 25473. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: AHD, CL, MG, MPD Related: 4omg, 4omh, 6ggi, 6ggj, 6ggk, 6ggl Gene: CotB2 (ATCC 25473) Activity: Lyase, with EC number 4.2.3.146 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 Terpene synthases generate terpenes employing diversified carbocation chemistry, including highly specific ring formations, proton and hydride transfers, and methyl as well as methylene migrations, followed by reaction quenching. In this enzyme family, the main catalytic challenge is not rate enhancement, but rather structural and reactive control of intrinsically unstable carbocations in order to guide the resulting product distribution. Here we employ multiscale modeling within classical and quantum dynamics frameworks to investigate the reaction mechanism in the diterpene synthase CotB2, commencing with the substrate geranyl geranyl diphosphate and terminating with the carbocation precursor to the final product cyclooctat-9-en-7-ol. The 11-step in-enzyme carbocation cascade is compared with the same reaction in the absence of the enzyme. Remarkably, the free energy profiles in gas phase and in CotB2 are surprisingly similar. This similarity contrasts the multitude of strong pi-cation, dipole-cation, and ion-pair interactions between all intermediates in the reaction cascade and the enzyme, suggesting a remarkable balance of interactions in CotB2. We ascribe this balance to the similar magnitude of the interactions between the carbocations along the reaction coordinate and the enzyme environment. The effect of CotB2 mutations is studied using multiscale mechanistic docking, machine learning, and X-ray crystallography, pointing the way for future terpene synthase design. The Impression of a Nonexisting Catalytic Effect: The Role of CotB2 in Guiding the Complex Biosynthesis of Cyclooctat-9-en-7-ol.,Raz K, Driller R, Dimos N, Ringel M, Bruck T, Loll B, Major DT J Am Chem Soc. 2020 Dec 8. doi: 10.1021/jacs.0c11348. PMID:33289561 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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