4YML
Crystal structure of Escherichia coli 5'-methylthioadenosine/S-adenosyl homocysteine nucleosidase (MTAN) complexed with (3S,4R)-methylthio-DADMe-Immucillin-A
Summary for 4YML
| Entry DOI | 10.2210/pdb4yml/pdb |
| Related | 1Y6Q 4WKC |
| Descriptor | 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase, (3S,4R)-1-[(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]-4-[(methylsulfanyl)methyl]pyrrolidin-3-ol, PHOSPHATE ION, ... (4 entities in total) |
| Functional Keywords | hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Escherichia coli |
| Total number of polymer chains | 1 |
| Total formula weight | 26447.06 |
| Authors | Cameron, S.A.,Thomas, K.,Almo, S.C.,Schramm, V.L. (deposition date: 2015-03-06, release date: 2015-08-26, Last modification date: 2023-09-27) |
| Primary citation | Evans, G.B.,Cameron, S.A.,Luxenburger, A.,Guan, R.,Suarez, J.,Thomas, K.,Schramm, V.L.,Tyler, P.C. Tight binding enantiomers of pre-clinical drug candidates. Bioorg.Med.Chem., 23:5326-5333, 2015 Cited by PubMed Abstract: 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. PubMed: 26260335DOI: 10.1016/j.bmc.2015.07.059 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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