5wpj

Structure of the class II 3-hydroxy-3-methylglutaryl-CoA reductase from Streptococcus pneumoniae bound to NADPH in open conformations

spinqualitylabelsall models 5wpj, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5wpj is a 4 chain structure with sequence from Streptococcus pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: GOL, NDP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8DNS5_STRR6 Publication Abstract from PubMed The key mevalonate pathway enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR) uses the cofactor NAD(P)H to reduce HMG-CoA to mevalonate in the production of countless metabolites and natural products. Although inhibition of HMGR by statin drugs is well-understood, several mechanistic details of HMGR catalysis remain unresolved, and the structural basis for the wide range of cofactor specificity for either NADH or NADPH among HMGRs from different organisms is also unknown. Here, we present crystal structures of HMGR from Streptococcus pneumoniae (SpHMGR) alongside kinetic data of the enzyme's cofactor preferences. Our structure of SpHMGR bound with its kinetically preferred NADPH cofactor suggests how NADPH-specific binding and recognition are achieved. In addition, our structure of HMG-CoA-bound SpHMGR reveals large, previously unknown conformational domain movements that may control HMGR substrate binding and enable cofactor exchange without intermediate release during the catalytic cycle. Taken together, this work provides critical new insights into both the HMGR reaction mechanism and the structural basis of cofactor specificity. Structural Features and Domain Movements Controlling Substrate Binding and Cofactor Specificity in Class II HMG-CoA Reductase.,Miller BR, Kung Y Biochemistry. 2018 Feb 6;57(5):654-662. doi: 10.1021/acs.biochem.7b00999. Epub, 2017 Dec 21. PMID:29224355 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also HMG-CoA Reductase 3D structures

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