7lnn | pdb_00007lnn

E. coli S-adenosyl methionine transferase co-crystallized with guanosine-5'-imidotriphosphate

spinqualitylabelsall models 7lnn, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7lnn is a 2 chain structure with sequence from Escherichia coli 908573. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, MG, PO4, PPK Gene: metK, HMPREF1611_00479 (Escherichia coli 908573) Activity: Methionine adenosyltransferase, with EC number 2.5.1.6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [V0ZE41_ECOLX] Catalyzes the formation of S-adenosylmethionine (AdoMet) from methionine and ATP. The overall synthetic reaction is composed of two sequential steps, AdoMet formation and the subsequent tripolyphosphate hydrolysis which occurs prior to release of AdoMet from the enzyme.[HAMAP-Rule:MF_00086] Publication Abstract from PubMed Protein conformational changes can facilitate the binding of noncognate substrates and underlying promiscuous activities. However, the contribution of substrate conformational dynamics to this process is comparatively poorly understood. Here, we analyze human (hMAT2A) and Escherichia coli (eMAT) methionine adenosyltransferases that have identical active sites but different substrate specificity. In the promiscuous hMAT2A, noncognate substrates bind in a stable conformation to allow catalysis. In contrast, noncognate substrates sample stable productive binding modes less frequently in eMAT owing to altered mobility in the enzyme active site. Different cellular concentrations of substrates likely drove the evolutionary divergence of substrate specificity in these orthologues. The observation of catalytic promiscuity in hMAT2A led to the detection of a new human metabolite, methyl thioguanosine, that is produced at elevated levels in a cancer cell line. This work establishes that identical active sites can result in different substrate specificity owing to the effects of substrate and enzyme dynamics. Substrate Dynamics Contribute to Enzymatic Specificity in Human and Bacterial Methionine Adenosyltransferases.,Gade M, Tan LL, Damry AM, Sandhu M, Brock JS, Delaney A, Villar-Briones A, Jackson CJ, Laurino P JACS Au. 2021 Nov 19;1(12):2349-2360. doi: 10.1021/jacsau.1c00464. eCollection, 2021 Dec 27. PMID:34977903 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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