6IGA

Crystal structure of argininosuccinate lyase from Mycobacterium tuberculosis

6IGA の概要

• エントリーDOI: 10.2210/pdb6iga/pdb
• 分子名称: Argininosuccinate lyase, SULFATE ION (2 entities in total)
• 機能のキーワード: argininosuccinate lyase, fumarate, tetramer, lyase
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 199408.69

構造登録者

Chen, X.B.,Liu, X. (登録日: 2018-09-25, 公開日: 2019-02-06, 最終更新日: 2023-11-22)

主引用文献

Chen, X.B.,Chen, J.,Zhang, W.,Wang, H.,Liu, X.,Zhou, W.,Yang, H.,Rao, Z.
Crystal structure and biochemical study on argininosuccinate lyase from Mycobacterium tuberculosis.
Biochem. Biophys. Res. Commun., 510:116-121, 2019

PubMed Abstract: Argininosuccinate lyase (ASL) participates in arginine synthesis through catalysing a reversible reaction in which argininosuccinate (AS) converts into arginine and fumarate. ASL from Mycobacterium tuberculosis is essential for its growth. In this work, the crystal structure of the apo form of MtbASL was determined and reveals a tetrameric structure that is essential for its activity since the active sites are formed by residues from three different monomers. Subsequently, we determined the crystal structure of MtbASL-sulfate complex, and the ligand mimics the negatively charged intermediate. The complex structure and mutagenesis studies indicate that residues S282 and H161 might act as a catalytic dyad. A major conformational change in the MtbASL-SO complex structure could be observed upon sulfate binding, and this movement facilitates the interaction between substrate and the residues involved in catalysis. A different conformational change in the C-terminal domain could be observed in the MtbASL-SO complex compared with that in other homologues. This difference may be responsible for the lower activity of MtbASL, which is related to the slow growth rate of M. tuberculosis. The C-terminal domain is a potential allosteric site upon inhibitor binding. The various conformational changes and the diversity of the sequence of the potential allosteric site across the homologues might provide clues for designing selective inhibitors against M. tuberculosis.

PubMed: 30665717
DOI: 10.1016/j.bbrc.2019.01.061

実験手法

X-RAY DIFFRACTION (2.776 Å)