Experimental identification and computational characterization of a novel extracellular metalloproteinase produced by Clostridium sordellii

RSC Advances
Michael J AldapeDong Xu

Abstract

Clostridium sordellii is a lethal pathogen for both animals and humans. Severe capillary leakage, toxic shock syndrome, and an extreme leukemoid reaction (LR), are hallmark features of C. sordellii infections and contribute to its high mortality rate. Here we report the discovery of a previously unknown and uncharacterized metalloproteinase of C. sordellii (referred as Mcs1) that cleaves human vascular cell adhesion molecule (VCAM)-1 in vitro, an adhesion molecule critical to hematopoietic precursor retention and leukocyte diapedesis. We successfully identified the open reading frame encoding Mcs1 within the ATCC 9714 genome and developed an Δmcs1 mutant strain using the ClosTron mutagenesis technology. No VCAM-1 proteolysis was observed from exotoxins collected from mutant strain cultures. Using advanced protein structural modeling and molecular dynamics simulation techniques, the 3D molecular structure and conformational features of Mcs1 were also characterized. Our data demonstrates that Mcs1 proteolytic activity is controlled by the electrostatic interactions between Glu113 and Arg227 residues and the gating motions within its cleft region. This pilot interdisciplinary investigation provided crucial experimental evidence of...Continue Reading

References

Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Mar 16, 2000·Microbes and Infection·S Miyoshi, S Shinoda
Nov 20, 2002·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Christian SinaveEric Deland
Nov 24, 2004·Southern Medical Journal·Mark A MarinellaRonald J Markert
Nov 25, 2004·Antimicrobial Agents and Chemotherapy·Magdalena Sieprawska-LupaJan Potempa
Oct 8, 2005·Journal of Computational Chemistry·Jay L BanksRonald M Levy
Apr 14, 2006·The New England Journal of Medicine·Etienne-Emile Baulieu
Nov 1, 2006·Protein Science : a Publication of the Protein Society·Min-Yi Shen, Andrej Sali
Nov 4, 2006·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·M J AldapeD L Stevens
Feb 27, 2007·The American Journal of Pathology·Blandine GenyMichel R Popoff
May 12, 2007·The Journal of Infectious Diseases·Michael John AldapeDennis Leroy Stevens
Jul 31, 2007·Journal of Microbiological Methods·John T HeapNigel P Minton
Apr 29, 2008·Nucleic Acids Research·Mark JohnsonThomas L Madden
Feb 4, 2009·Infection and Immunity·Katherine J LauderdaleAlexander R Horswill
Aug 1, 2009·Circulation Research·William A Muller
Apr 20, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alexander J LaarmanSuzan H M Rooijakkers
Jun 5, 2012·Nucleic Acids Research·Panu ArtimoHeinz Stockinger
Jun 12, 2013·Nucleic Acids Research·Daniel W A BuchanDavid T Jones
Sep 10, 2014·Current Protocols in Bioinformatics·Benjamin Webb, Andrej Sali
Dec 18, 2015·Nucleic Acids Research·Robert D FinnAlex Bateman

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPase
GTPases
PCR
gene knockout

Software Mentioned

Protein
MAESTRO
Schrodinger suite
Modeller
PROPKA
ClosTron
OPLS
VMD
PSI
Expasy Proteomics Server

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Related Papers

The Lancet Infectious Diseases
David M Aronoff, Jimmy D Ballard
Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
R V SperaS L Allen
© 2022 Meta ULC. All rights reserved