4i56

HMG-CoA reductase from pseudomonas mevalonii complexed with dithio-HMG-coa

spinqualitylabelsall models 4i56, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4i56 is a 2 chain structure with sequence from Pseudomonas mevalonii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.5Å Ligands: 1CZ, GOL, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MVAA_PSEMV P.mevalonii can use mevalonate as sole carbon source. With this enzyme mevalonate is deacetylated to HMG-CoA. Publication Abstract from PubMed In this study we take advantage of the ability of HMG-CoA reductase (HMGR) from Pseudomonas mevalonii to remain active while in crystallized form to study the changing interactions between the ligands and protein as the first reaction intermediate is created. HMG-CoA reductase catalyzes one of the few double oxidation/reduction reactions in intermediary metabolism that take place in a single active site. Our laboratory has undertaken an exploration of this reaction space using structures of HMG-CoA reductase complexed with various substrate, nucleotide, product, and inhibitor combinations. Focusing in this publication on the first hydride transfer, our structures follow this reduction reaction as the enzyme converts the HMG-CoA thioester from a flat sp2 like geometry to a pyramidal thiohemiacetal configuration consistent with a transition to an sp3 orbital. This change in the geometry propagates through the CoA ligand whose first amide bond is rotated 180 degrees where it anchors a web of hydrogen bonds that weave together the nucleotide, the reaction intermediate, the enzyme and the catalytic residues. This creates a stable intermediate structure prepared for nucleotide exchange and the second reduction reaction within the HMG-CoA reductase active site. Identification of this reaction intermediate provides a template for the development of an inhibitor that would act as an antibiotic effective against the HMG-CoA reductase of methicillin-resistant Staphylococcus aureus. A novel role for CoA during hydride transfer in 3-hydroxy-3-methylglutaryl-coenzyme A reductase.,Steussy CN, Critchelow CJ, Schmidt TJ, Min JK, Wrensford LV, Burgner JW, Rodwell VW, Stauffacher CV Biochemistry. 2013 Jun 26. PMID:23802607 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also HMG-CoA Reductase 3D structures

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