5uhu

Solution conformation of cytochrome P450 MycG with mycinamicin IV bound

spinqualitylabelsall models 5uhu Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5uhu is a 1 chain structure with sequence from Micromonospora griseorubida. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, models Ligands: HEM, MIV Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MYCG_MICGR Involved in the biosynthesis of mycinamicin, a 16-membered macrolide antibiotic. Catalyzes consecutive hydroxylation (at C14) and epoxidation (at C12-C13) reactions with mycinamicin IV as initial substrate, leading to mycinamicin II. These reactions require prior dimethylation of 6-deoxyallose to mycinose for effective conversion by the dual function MycG enzyme. Publication Abstract from PubMed MycG is a P450 monooxygenase that catalyzes the sequential hydroxylation and epoxidation of mycinamicin IV (M-IV), the last two steps in the biosynthesis of mycinamicin II, a macrolide antibiotic isolated from Micromonospora griseorubida. The crystal structure of MycG with M-IV bound was previously determined but showed the bound substrate in an orientation that did not rationalize the observed regiochemistry of M-IV hydroxylation. Nuclear magnetic resonance paramagnetic relaxation enhancements provided evidence of an orientation of M-IV in the MycG active site more compatible with the observed chemistry, but substrate-induced changes in the enzyme structure were not characterized. We now describe the use of amide 1H-15N residual dipolar couplings as experimental restraints in solvated "soft annealing" molecular dynamics simulations to generate solution structural ensembles of M-IV-bound MycG. Chemical shift perturbations, hydrogen-deuterium exchange, and 15N relaxation behavior provide insight into the dynamic and electronic perturbations in the MycG structure in response to M-IV binding. The solution and crystallographic structures are compared, and the possibility that the crystallographic orientation of bound M-IV represents an inhibitory mode is discussed. Solution Conformations and Dynamics of Substrate-Bound Cytochrome P450 MycG.,Tietz DR, Podust LM, Sherman DH, Pochapsky TC Biochemistry. 2017 May 30;56(21):2701-2714. doi: 10.1021/acs.biochem.7b00291., Epub 2017 May 16. PMID:28488849 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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