5UGQ

Crystal Structure of Hip1 (Rv2224c)

5UGQ の概要

• エントリーDOI: 10.2210/pdb5ugq/pdb
• 分子名称: Carboxylesterase A (2 entities in total)
• 機能のキーワード: serine protease, hydrolase
• 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: 53359.35

構造登録者

Naffin-Olivos, J.L.,Daab, A.,White, A.,Goldfarb, N.,Milne, A.C.,Liu, D.,Dunn, B.M.,Rengarajan, J.,Petsko, G.A.,Ringe, D. (登録日: 2017-01-09, 公開日: 2017-04-12, 最終更新日: 2024-10-09)

主引用文献

Naffin-Olivos, J.L.,Daab, A.,White, A.,Goldfarb, N.E.,Milne, A.C.,Liu, D.,Baikovitz, J.,Dunn, B.M.,Rengarajan, J.,Petsko, G.A.,Ringe, D.
Structure Determination of Mycobacterium tuberculosis Serine Protease Hip1 (Rv2224c).
Biochemistry, 56:2304-2314, 2017

PubMed Abstract: The Mycobacterium tuberculosis (Mtb) serine protease Hip1 (hydrolase important for pathogenesis; Rv2224c) promotes tuberculosis (TB) pathogenesis by impairing host immune responses through proteolysis of a protein substrate, Mtb GroEL2. The cell surface localization of Hip1 and its immunomodulatory functions make Hip1 a good drug target for new adjunctive immune therapies for TB. Here, we report the crystal structure of Hip1 to a resolution of 2.6 Å and the kinetic studies of the enzyme against model substrates and the protein GroEL2. The structure shows a two-domain protein, one of which contains the catalytic residues that are the signature of a serine protease. Surprisingly, a threonine is located within the active site close enough to hydrogen bond with the catalytic residues Asp463 and His490. Mutation of this residue, Thr466, to alanine established its importance for function. Our studies provide insights into the structure of a member of a novel family of proteases. Knowledge of the Hip1 structure will aid in designing inhibitors that could block Hip1 activity.

PubMed: 28346784
DOI: 10.1021/acs.biochem.6b01066

実験手法

X-RAY DIFFRACTION (2.609 Å)