Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Evans GB, Cameron SA, Luxenburger A, Guan R, Suarez J, Thomas K, Schramm VL, Tyler PC. Tight binding enantiomers of pre-clinical drug candidates. Bioorg Med Chem. 2015 Jul 30. pii: S0968-0896(15)00643-4. doi:, 10.1016/j.bmc.2015.07.059. PMID:26260335 doi:http://dx.doi.org/10.1016/j.bmc.2015.07.059
