4PR3

Crystal structure of Brucella melitensis 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase

4PR3 の概要

• エントリーDOI: 10.2210/pdb4pr3/pdb
• 分子名称: 5'-methylthioadenosine nucleosidase / s-adenosylhomocysteine nucleosidase, ADENINE, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: mixed alpha/beta, hydrolase
• 由来する生物種: Brucella melitensis bv. 1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 50963.32

構造登録者

Zhang, X.C.,Kang, X.S.,Zhao, Y.,Jiang, D.H.,Li, X.M.,Chen, Z.L. (登録日: 2014-03-05, 公開日: 2014-04-30, 最終更新日: 2024-10-30)

主引用文献

Kang, X.S.,Zhao, Y.,Jiang, D.H.,Li, X.M.,Wang, X.P.,Wu, Y.,Chen, Z.L.,Zhang, X.C.
Crystal structure and biochemical studies of Brucella melitensis 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase
Biochem.Biophys.Res.Commun., 446:965-970, 2014

PubMed Abstract: The prokaryotic 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) catalyzes the irreversible cleavage of the glycosidic bond in 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH), a process that plays a key role in several metabolic pathways. Its absence in all mammalian species has implicated this enzyme as a promising target for antimicrobial drug design. Here, we report the crystal structure of BmMTAN in complex with its product adenine at a resolution of 2.6 Å determined by single-wavelength anomalous dispersion method. 11 key residues were mutated for kinetic characterization. Mutations of Tyr134 and Met144 resulted in the largest overall increase in Km, whereas mutagenesis of residues Glu18, Glu145 and Asp168 completely abolished activity. Glu145 and Asp168 were identified as active site residues essential for catalysis. The catalytic mechanism and implications of this structure for broad-based antibiotic design are discussed.

PubMed: 24657441
DOI: 10.1016/j.bbrc.2014.03.045

実験手法

X-RAY DIFFRACTION (2.606 Å)