Identifying common metalloprotease inhibitors by protein fold types using Fourier transform mass spectrometry

Jennifer K Mitchell; Desley Pitcher; Bernadette M McArdle; Terese Alnefelt; Sandra Duffy; Vicky Avery; Ronald J Quinn

doi:10.1016/j.bmcl.2007.09.084

Identifying common metalloprotease inhibitors by protein fold types using Fourier transform mass spectrometry

Bioorg Med Chem Lett. 2007 Dec 1;17(23):6521-4. doi: 10.1016/j.bmcl.2007.09.084. Epub 2007 Sep 29.

Authors

Jennifer K Mitchell¹, Desley Pitcher, Bernadette M McArdle, Terese Alnefelt, Sandra Duffy, Vicky Avery, Ronald J Quinn

Affiliation

¹ Eskitis Institute, Griffith University, Brisbane, Qld 4111, Australia.

PMID: 17933532
DOI: 10.1016/j.bmcl.2007.09.084

Abstract

Fourteen natural products, known to inhibit other proteins of the Zincin-like fold class, were screened for inhibition of the Zincin-like fold metalloprotease thermolysin using mass spectrometry. Fourier Transform Mass Spectrometry was successful in identifying actinonin, a known inhibitor of astacin and stromelysin, to be an inhibitor of thermolysin. Molecular modelling studies have shown that specificity within the Zincin-like fold is determined by Protein Fold Topology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemistry, Pharmaceutical / methods
Hydroxamic Acids / chemistry
Hydroxamic Acids / metabolism
Mass Spectrometry / methods
Metalloproteases / antagonists & inhibitors*
Protease Inhibitors / analysis
Protease Inhibitors / chemistry*
Protein Folding*
Proteins / analysis
Proteins / chemistry*
Spectroscopy, Fourier Transform Infrared / methods
Thermolysin / chemistry
Thermolysin / metabolism

Substances

Hydroxamic Acids
Protease Inhibitors
Proteins
Metalloproteases
Thermolysin
actinonin