3RIM

Crystal structure of mycobacterium tuberculosis Transketolase (Rv1449c)

3RIM の概要

• エントリーDOI: 10.2210/pdb3rim/pdb
• 分子名称: Transketolase, MAGNESIUM ION, THIAMINE DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: transketolase, mycobacterium, tpp, transferase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 305209.48

構造登録者

Pojer, F.,Fullam, E.,Jones, T.A.,Cole, S.T. (登録日: 2011-04-14, 公開日: 2012-02-29, 最終更新日: 2023-09-13)

主引用文献

Fullam, E.,Pojer, F.,Bergfors, T.,Jones, T.A.,Cole, S.T.
Structure and function of the transketolase from Mycobacterium tuberculosis and comparison with the human enzyme.
Open Biol, 2:110026-110026, 2012

PubMed Abstract: The transketolase (TKT) enzyme in Mycobacterium tuberculosis represents a novel drug target for tuberculosis treatment and has low homology with the orthologous human enzyme. Here, we report on the structural and kinetic characterization of the transketolase from M. tuberculosis (TBTKT), a homodimer whose monomers each comprise 700 amino acids. We show that TBTKT catalyses the oxidation of donor sugars xylulose-5-phosphate and fructose-6-phosphate as well as the reduction of the acceptor sugar ribose-5-phosphate. An invariant residue of the TKT consensus sequence required for thiamine cofactor binding is mutated in TBTKT; yet its catalytic activities are unaffected, and the 2.5 Å resolution structure of full-length TBTKT provides an explanation for this. Key structural differences between the human and mycobacterial TKT enzymes that impact both substrate and cofactor recognition and binding were uncovered. These changes explain the kinetic differences between TBTKT and its human counterpart, and their differential inhibition by small molecules. The availability of a detailed structural model of TBTKT will enable differences between human and M. tuberculosis TKT structures to be exploited to design selective inhibitors with potential antitubercular activity.

PubMed: 22645655
DOI: 10.1098/rsob.110026

実験手法

X-RAY DIFFRACTION (2.49 Å)