2JJE

Crystal structure of T330S mutant of Rv3290c from M. tuberculosis

2JJE の概要

• エントリーDOI: 10.2210/pdb2jje/pdb
• 関連するPDBエントリー: 2JJF 2JJG 2JJH
• 分子名称: L-LYSINE EPSILON AMINOTRANSFERASE, PYRIDOXAL-5'-PHOSPHATE (3 entities in total)
• 機能のキーワード: aminotransferase, pyridoxal phosphate, plp, rv3290c, transferase, t330s mutant, lysine amino transferase, mycobacterium tuberculosis
• 由来する生物種: MYCOBACTERIUM TUBERCULOSIS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 49302.09

構造登録者

Tripathi, S.M.,Ramachandran, R. (登録日: 2008-04-03, 公開日: 2009-06-30, 最終更新日: 2025-04-09)

主引用文献

Tripathi, S.M.,Agarwal, A.,Ramachandran, R.
Mutational Analysis of Mycobacterium Tuberculosis Lysine Epsilon-Aminotransferase and Inhibitor Co-Crystal Structures, Reveals Distinct Binding Modes.
Biochem.Biophys.Res.Commun., 463:154-, 2015

PubMed Abstract: Lysine ɛ-aminotransferase (LAT) converts lysine to α-aminoadipate-δ-semialdehyde in a PLP-mediated reaction. We mutated active-site T330, N328 and E243, and structurally rationalized their properties. T330A and T330S mutants cannot bind PLP and are inactive. N328A although inactive, binds to PLP. E243A retains activity, but binds α-ketoglutarate in a different conformation. We had earlier identified 2-aminomethyl piperidine derivative as a LAT inhibitor. The co-crystal structure reveals that it mimics binding of C5 substrates and exhibits two binding modes. E243, that shields R422 in the apo enzyme, exhibits conformational changes to permit the binding of the inhibitor in one of the binding modes. Structure-based analysis of bound water in the active site suggests optimization strategies for synthesis of improved inhibitors.

PubMed: 26003725
DOI: 10.1016/J.BBRC.2015.05.055

実験手法

X-RAY DIFFRACTION (2.2 Å)