5ugh

Crystal structure of Mat2a bound to the allosteric inhibitor PF-02929366

spinqualitylabelsall models 5ugh, resolution 2.06Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ugh is a 4 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 2.062Å Ligands: 8AJ Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function METK2_HUMAN Catalyzes the formation of S-adenosylmethionine from methionine and ATP. Publication Abstract from PubMed S-Adenosyl-L-methionine (SAM) is an enzyme cofactor used in methyl transfer reactions and polyamine biosynthesis. The biosynthesis of SAM from ATP and L-methionine is performed by the methionine adenosyltransferase enzyme family (Mat; EC 2.5.1.6). Human methionine adenosyltransferase 2A (Mat2A), the extrahepatic isoform, is often deregulated in cancer. We identified a Mat2A inhibitor, PF-9366, that binds an allosteric site on Mat2A that overlaps with the binding site for the Mat2A regulator, Mat2B. Studies exploiting PF-9366 suggested a general mode of Mat2A allosteric regulation. Allosteric binding of PF-9366 or Mat2B altered the Mat2A active site, resulting in increased substrate affinity and decreased enzyme turnover. These data support a model whereby Mat2B functions as an inhibitor of Mat2A activity when methionine or SAM levels are high, yet functions as an activator of Mat2A when methionine or SAM levels are low. The ramification of Mat2A activity modulation in cancer cells is also described. Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A.,Quinlan CL, Kaiser SE, Bolanos B, Nowlin D, Grantner R, Karlicek-Bryant S, Feng JL, Jenkinson S, Freeman-Cook K, Dann SG, Wang X, Wells PA, Fantin VR, Stewart AE, Grant SK Nat Chem Biol. 2017 Jul;13(7):785-792. doi: 10.1038/nchembio.2384. Epub 2017 May , 29. PMID:28553945 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also S-adenosylmethionine synthetase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA