7rxx

Human Methionine Adenosyltransferase 2A bound to Methylthioadenosine and two sulfate in the active site

spinqualitylabelsall models 7rxx, resolution 1.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7rxx is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.25Å Ligands: ALA, EDO, K, MG, MTA, NA, P3G, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function METK2_HUMAN Catalyzes the formation of S-adenosylmethionine from methionine and ATP. Publication Abstract from PubMed Human methionine adenosyltransferase MAT2A provides S-adenosyl-l-methionine (AdoMet) for methyl-transfer reactions. Epigenetic methylations influence expression patterns in development and in cancer. Transition-state analysis and kinetic studies have described the mechanism of AdoMet and triphosphate formation at the catalytic site. Hydrolysis of triphosphate to pyrophosphate and phosphate by MAT2A is required for product release and proceeds through a second chemical transition state. Crystal structures of MAT2A with analogues of AdoMet and pyrophosphate were obtained in the presence of Mg(2+), Al(3+), and F(-). MgF3(-) is trapped as a PO3(-) mimic in a structure with malonate filling the pyrophosphate site. NMR demonstrates that MgF3(-) and AlF3(0) are bound by MAT2A as mimics of the departing phosphoryl group. Crystallographic analysis reveals a planar MgF3(-) acting to mimic a phosphoryl (PO3(-)) leaving group. The modeled transition state with PO3(-) has the phosphorus atom sandwiched symmetrically and equidistant (approximately 2 A) between a pyrophosphate oxygen and the water nucleophile. A catalytic site arginine directs the nucleophilic water to the phosphoryl leaving group. The catalytic geometry of the transition-state reconstruction predicts a loose transition state with characteristics of symmetric nucleophilic displacement. Mechanism of Triphosphate Hydrolysis by Human MAT2A at 1.07 A Resolution.,Ghosh A, Niland CN, Cahill SM, Karadkhelkar NM, Schramm VL J Am Chem Soc. 2021 Oct 20. doi: 10.1021/jacs.1c09328. PMID:34668717 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also S-adenosylmethionine synthetase 3D structures

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