4yml | pdb_00004yml

Crystal structure of Escherichia coli 5'-methylthioadenosine/S-adenosyl homocysteine nucleosidase (MTAN) complexed with (3S,4R)-methylthio-DADMe-Immucillin-A

spinqualitylabelsall models 4yml, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4yml is a 1 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.75Å Ligands: 4F0, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MTNN_ECOLI Catalyzes the irreversible cleavage of the glycosidic bond in both 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH/AdoHcy) to adenine and the corresponding thioribose, 5'-methylthioribose and S-ribosylhomocysteine, respectively. Can also use 5'-isobutylthioadenosine, 5'-n-butylthioadenosine, S-adenosyl-D-homocysteine, decarboxylated adenosylhomocysteine, deaminated adenosylhomocysteine and S-2-aza-adenosylhomocysteine as substrates.[HAMAP-Rule:MF_01684] Publication Abstract from PubMed MTDIA is a picomolar transition state analogue inhibitor of human methylthioadenosine phosphorylase and a femtomolar inhibitor of Escherichia coli methylthioadenosine nucleosidase. MTDIA has proven to be a non-toxic, orally available pre-clinical drug candidate with remarkable anti-tumour activity against a variety of human cancers in mouse xenografts. The structurally similar compound MTDIH is a potent inhibitor of human and malarial purine nucleoside phosphorylase (PNP) as well as the newly discovered enzyme, methylthioinosine phosphorylase, isolated from Pseudomonas aeruginosa. Since the enantiomers of some pharmaceuticals have revealed surprising biological activities, the enantiomers of MTDIH and MTDIA, compounds 1 and 2, respectively, were prepared and their enzyme binding properties studied. Despite binding less tightly to their target enzymes than their enantiomers compounds 1 and 2 are nanomolar inhibitors. Tight binding enantiomers of pre-clinical drug candidates.,Evans GB, Cameron SA, Luxenburger A, Guan R, Suarez J, Thomas K, Schramm VL, Tyler PC Bioorg Med Chem. 2015 Jul 30. pii: S0968-0896(15)00643-4. doi:, 10.1016/j.bmc.2015.07.059. PMID:26260335 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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