5UOH

Crystal Structure of Hip1 (Rv2224c) T466A mutant

Summary for 5UOH

• Entry DOI: 10.2210/pdb5uoh/pdb
• Related: 5UNO
• Descriptor: Carboxylesterase A (1 entity in total)
• Functional Keywords: serine protease, hydrolase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 1
• Total formula weight: 52954.17

Authors

Naffin-Olivos, J.L.,Daab, A.,White, A.,Goldfarb, N.,Milne, A.C.,Liu, D.,Baikovitz, J.,Dunn, B.M.,Rengarajan, J.,Petsko, G.A.,Ringe, D. (deposition date: 2017-01-31, release date: 2017-04-12, Last modification date: 2024-10-09)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.609 Å)