5gme

Crystal structure of Sulfolobus solfataricus Diphosphomevalonate decarboxylase in complex with ADP

spinqualitylabelsall models 5gme, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5gme is a 1 chain structure with sequence from Saccharolobus solfataricus P2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Ligands: ADP, AMP, DP6, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DMD_SACS2 Catalyzes the decarboxylation of mevalonate 5-diphosphate (MVAPP) to isopentenyl diphosphate (IPP). Functions in the mevalonate (MVA) pathway leading to IPP, a key precursor for the biosynthesis of isoprenoid compounds such as archaeal membrane lipids. Publication Abstract from PubMed The biosynthesis of isopentenyl diphosphate, a fundamental precursor for isoprenoids, via the mevalonate pathway is completed by diphosphomevalonate decarboxylase. This enzyme catalyzes the formation of isopentenyl diphosphate through the ATP-dependent phosphorylation of the 3-hydroxyl group of (R)-5-diphosphomevalonate followed by decarboxylation coupled with the elimination of the 3-phosphate group. In this reaction, a conserved aspartate residue has been proposed to be involved in the phosphorylation step as the general base catalyst that abstracts a proton from the 3-hydroxyl group. In this study, the catalytic mechanism of this rare type of decarboxylase is re-investigated by structural and mutagenic studies on the enzyme from a thermoacidophilic archaeon Sulfolobus solfataricus The crystal structures of the archaeal enzyme in complex with (R)-5-diphosphomevalonate and adenosine 5'-O-(3-thio)triphosphate or with (R)-5-diphosphomevalonate and ADP are newly solved, and theoretical analysis based on the structure suggests the inability of proton abstraction by the conserved aspartate residue, Asp-281. Site-directed mutagenesis on Asp-281 creates mutants that only show diphosphomevalonate 3-kinase activity, demonstrating that the residue is required in the process of phosphate elimination/decarboxylation, rather than in the preceding phosphorylation step. These results enable discussion of the catalytic roles of the aspartate residue and provide clear proof of the involvement of a long predicted intermediate, (R)-3-phospho-5-diphosphomevalonate, in the reaction of the enzyme. A Single Amino Acid Mutation Converts (R)-5-Diphosphomevalonate Decarboxylase into a Kinase.,Motoyama K, Unno H, Hattori A, Takaoka T, Ishikita H, Kawaide H, Yoshimura T, Hemmi H J Biol Chem. 2017 Feb 10;292(6):2457-2469. doi: 10.1074/jbc.M116.752535. Epub, 2016 Dec 21. PMID:28003359 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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