6eeu | pdb_00006eeu

Structure of class II HMG-CoA reductase from Delftia acidovorans

spinqualitylabelsall models 6eeu, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6eeu is a 1 chain structure with sequence from "pseudomonas_desmolytica"_gray_and_thornton_1928 "pseudomonas desmolytica" gray and thornton 1928. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, SO4 Gene: Daci_0287 ("Pseudomonas desmolytica" Gray and Thornton 1928) Activity: Hydroxymethylglutaryl-CoA reductase, with EC number 1.1.1.88 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR) catalyzes the first committed step of the mevalonate pathway, which is used across biology in the biosynthesis of countless metabolites. HMGR consumes 2 equiv of the cofactor NAD(P)H to perform the four-electron reduction of HMG-CoA to mevalonate toward the production of steroids and isoprenoids, the largest class of natural products. Recent structural data have shown that HMGR contains a highly mobile C-terminal domain (CTD) that is believed to adopt many different conformations to permit binding and dissociation of the substrate, cofactors, and products at specific points during the reaction cycle. Here, we have characterized the HMGR from Delftia acidovorans as an NADH-specific enzyme and determined crystal structures of the enzyme in unbound, mevalonate-bound, and NADH- and citrate-bound states. Together, these structures depict ligand binding in both the active site and the cofactor-binding site while illustrating how a conserved helical motif confers NAD(P)H cofactor specificity. Unexpectedly, the NADH-bound structure also reveals a new conformation of the CTD, in which the domain has "flipped" upside-down, while directly binding the cofactor. By capturing these structural snapshots, this work not only expands the known range of HMGR domain movement but also provides valuable insight into the catalytic mechanism of this biologically important enzyme. New Crystallographic Snapshots of Large Domain Movements in Bacterial 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase.,Ragwan ER, Arai E, Kung Y Biochemistry. 2018 Sep 19. doi: 10.1021/acs.biochem.8b00869. PMID:30199631 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also HMG-CoA Reductase 3D structures

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