the active site residue V266 of Chlamydial HtrA is critical for substrate binding during both in vitro and in vivo conditions

Journal of Molecular Microbiology and Biotechnology
Sarina GloecklWilhelmina M Huston

Abstract

HtrA is a complex, multimeric chaperone and serine protease important for the virulence and survival of many bacteria. Chlamydia trachomatis is an obligate, intracellular bacterial pathogen that is responsible for severe disease pathology. C. trachomatis HtrA (CtHtrA) has been shown to be highly expressed in laboratory models of disease. In this study, molecular modelling of CtHtrA protein active site structure identified putative S1-S3 subsite residues I242, I265, and V266. These residues were altered by site-directed mutagenesis, and these changes were shown to considerably reduce protease activity on known substrates and resulted in a narrower and distinct range of substrates compared to wild type. Bacterial two-hybrid analysis revealed that CtHtrA is able to interact in vivo with a broad range of protein sequences with high affinity. Notably, however, the interaction was significantly altered in 35 out of 69 clones when residue V266 was mutated, indicating that this residue has an important function during substrate binding.

References

Jan 1, 1996·Methods in Enzymology·J GarnierB Robson
Dec 16, 2003·Proceedings of the National Academy of Sciences of the United States of America·Robert J BellandHarlan D Caldwell
May 29, 2008·Proceedings of the National Academy of Sciences of the United States of America·Tobias KrojerTim Clausen
Jun 3, 2010·Archives of Biochemistry and Biophysics·Anna Sobiecka-SzkatulaJoanna Skorko-Glonek
Jun 29, 2010·Nature Structural & Molecular Biology·Tobias KrojerTim Clausen
Apr 27, 2011·Molecular Microbiology·Catherine BaudFrançoise Jacob-Dubuisson
Aug 2, 2011·Molecular Microbiology·Theodor ChitlaruAvigdor Shafferman

❮ Previous
Next ❯

Citations

Sep 16, 2018·International Journal of Molecular Sciences·Ami P RavalHelen M Bramlett
Jun 9, 2017·Future Microbiology·James W MarshWilhelmina M Huston
Aug 10, 2019·Bioorganic & Medicinal Chemistry·Ayodeji A AgbowuroJoel D A Tyndall

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anthrax Vaccines

Three different types of anthrax vaccines are available; a live-attenuated, an alum-precipitated cell-free filtrate and a protein recombinant vaccine. The effectiveness between the three is uncertain, but the live-attenuated have shown to reduce the risk of anthrax with low adverse events. Here is the latest research on anthrax vaccines.

Anthrax

Anthrax toxin, comprising protective antigen, lethal factor, and oedema factor, is the major virulence factor of Bacillus anthracis, an agent that causes high mortality in humans and animals. Here is the latest research on Anthrax.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Anthrax Vaccines (ASM)

Three different types of anthrax vaccines are available; a live-attenuated, an alum-precipitated cell-free filtrate and a protein recombinant vaccine. The effectiveness between the three is uncertain, but the live-attenuated have shown to reduce the risk of anthrax with low adverse events. Here is the latest research on anthrax vaccines.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.