1NC3

Crystal structure of E. coli MTA/AdoHcy nucleosidase complexed with formycin A (FMA)

1NC3 の概要

• エントリーDOI: 10.2210/pdb1nc3/pdb
• 関連するPDBエントリー: 1JYS 1NC1
• 分子名称: MTA/SAH nucleosidase, (1S)-1-(7-amino-1H-pyrazolo[4,3-d]pyrimidin-3-yl)-1,4-anhydro-D-ribitol (3 entities in total)
• 機能のキーワード: mixed alpha/beta dimer, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51510.73

構造登録者

Lee, J.E.,Cornell, K.A.,Riscoe, M.K.,Howell, P.L. (登録日: 2002-12-04, 公開日: 2003-03-25, 最終更新日: 2023-08-16)

主引用文献

Lee, J.E.,Cornell, K.A.,Riscoe, M.K.,Howell, P.L.
Structure of Escherichia coli 5'-methylthioadenosine/ S-adenosylhomocysteine nucleosidase inhibitor complexes provide insight into the conformational changes required for substrate binding and catalysis.
J.Biol.Chem., 278:8761-8770, 2003

PubMed Abstract: 5'-Methylthioadenosine/S-adenosylhomocysteine (MTA/AdoHcy) nucleosidase is a key enzyme in a number of critical biological processes in many microbes. This nucleosidase catalyzes the irreversible hydrolysis of the N(9)-C(1') bond of MTA or AdoHcy to form adenine and the corresponding thioribose. The key role of the MTA/AdoHcy nucleosidase in biological methylation, polyamine biosynthesis, methionine recycling, and bacterial quorum sensing has made it an important antimicrobial drug target. The crystal structures of Escherichia coli MTA/AdoHcy nucleosidase complexed with the transition state analog, formycin A (FMA), and the nonhydrolyzable substrate analog, 5'-methylthiotubercidin (MTT) have been solved to 2.2- and 2.0-A resolution, respectively. These are the first MTA/AdoHcy nucleosidase structures to be solved in the presence of inhibitors. These structures clearly identify the residues involved in substrate binding and catalysis in the active site. Comparisons of the inhibitor complexes to the adenine-bound MTA/AdoHcy nucleosidase (Lee, J. E., Cornell, K. A., Riscoe, M. K., and Howell, P. L. (2001) Structure (Camb.) 9, 941-953) structure provide evidence for a ligand-induced conformational change in the active site and the substrate preference of the enzyme. The enzymatic mechanism has been re-examined.

PubMed: 12496243
DOI: 10.1074/jbc.M210836200

実験手法

X-RAY DIFFRACTION (2.2 Å)