1SR9

Crystal Structure of LeuA from Mycobacterium tuberculosis

1SR9 の概要

• エントリーDOI: 10.2210/pdb1sr9/pdb
• 分子名称: 2-isopropylmalate synthase, ZINC ION, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: tim barrel, transferase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 141898.85

構造登録者

Koon, N.,Squire, C.J.,Baker, E.N. (登録日: 2004-03-22, 公開日: 2004-05-18, 最終更新日: 2024-11-20)

主引用文献

Koon, N.,Squire, C.J.,Baker, E.N.
Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in leucine biosynthesis
Proc.Natl.Acad.Sci.USA, 101:8295-8300, 2004

PubMed Abstract: The leucine biosynthetic pathway is essential for the growth of Mycobacterium tuberculosis and is a potential target for the design of new anti-tuberculosis drugs. The crystal structure of alpha-isopropylmalate synthase, which catalyzes the first committed step in this pathway, has been determined by multiwavelength anomalous dispersion methods and refined at 2.0-A resolution in complex with its substrate alpha-ketoisovalerate. The structure reveals a tightly associated, domain-swapped dimer in which each monomer comprises an (alpha/beta)(8) TIM barrel catalytic domain, a helical linker domain, and a regulatory domain of novel fold. Mutational and crystallographic data indicate the latter as the site for leucine feedback inhibition of activity. Domain swapping enables the linker domain of one monomer to sit over the catalytic domain of the other, inserting residues into the active site that may be important in catalysis. The alpha-ketoisovalerate substrate binds to an active site zinc ion, adjacent to a cavity that can accommodate acetyl-CoA. Sequence and structural similarities point to a catalytic mechanism similar to that of malate synthase and an evolutionary relationship with an aldolase that catalyzes the reverse reaction on a similar substrate.

PubMed: 15159544
DOI: 10.1073/pnas.0400820101

実験手法

X-RAY DIFFRACTION (2 Å)