3DTF

Structural analysis of mycobacterial branched chain aminotransferase- implications for inhibitor design

3DTF の概要

• エントリーDOI: 10.2210/pdb3dtf/pdb
• 関連するPDBエントリー: 3DTG 3DTH
• 分子名称: Branched-chain amino acid aminotransferase, SULFATE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: open twisted alpha/beta, aminotransferase, transferase
• 由来する生物種: Mycobacterium smegmatis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 81108.74

構造登録者

Castell, A.,Unge, T. (登録日: 2008-07-15, 公開日: 2009-06-23, 最終更新日: 2023-11-01)

主引用文献

Castell, A.,Mille, C.,Unge, T.
Structural analysis of mycobacterial branched-chain aminotransferase: implications for inhibitor design.
Acta Crystallogr.,Sect.D, 66:549-557, 2010

PubMed Abstract: The branched-chain aminotransferase (BCAT) of Mycobacterium tuberculosis has been characterized as being essential to the survival of the bacterium. The enzyme is pyridoxal 5'-phosphate-dependent and belongs to the aminotransferase IIIa subfamily, to which the human BCATs also belong. The overall sequence similarity is high within the subfamily and the sequence identity among the active-site residues is high. In order to identify structurally unique features of M. tuberculosis BCAT, X-ray structural and functional analyses of the closely related BCAT from M. smegmatis were carried out. The crystal structures include the apo form at 2.2 A resolution and a 1.9 A structure of the holo form cocrystallized with the inhibitor O-benzylhydroxylamine (Obe). The analyses highlighted the active-site residues Tyr209 and Gly243 as being structurally unique characteristics of the mycobacterial BCATs relative to the human BCATs. The inhibitory activities of Obe and ammonium sulfate were verified in an inhibition assay. Modelling of the inhibitor Obe in the substrate pocket indicated potential for the design of a mycobacterial-specific inhibitor.

PubMed: 20445230
DOI: 10.1107/S0907444910004877

実験手法

X-RAY DIFFRACTION (2.2 Å)