4YML

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

4YML の概要

• エントリーDOI: 10.2210/pdb4yml/pdb
• 関連するPDBエントリー: 1Y6Q 4WKC
• 分子名称: 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)
• 機能のキーワード: hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26447.06

構造登録者

Cameron, S.A.,Thomas, K.,Almo, S.C.,Schramm, V.L. (登録日: 2015-03-06, 公開日: 2015-08-26, 最終更新日: 2023-09-27)

主引用文献

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

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: 26260335
DOI: 10.1016/j.bmc.2015.07.059

実験手法

X-RAY DIFFRACTION (1.75 Å)