Identifying common metalloprotease inhibitors by protein fold types using Fourier transform mass spectrometry.
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.
Mitchell
Jennifer K
JK
Eskitis Institute, Griffith University, Brisbane, Qld 4111, Australia.
Pitcher
Desley
D
McArdle
Bernadette M
BM
Alnefelt
Terese
T
Duffy
Sandra
S
Avery
Vicky
V
Quinn
Ronald J
RJ
D002626:Chemistry, Pharmaceutical / Q000379:methods; D006877:Hydroxamic Acids / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D045726:Metalloproteases / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000032:analysis / Q000737:chemistry*; D017510:Protein Folding; D011506:Proteins / Q000032:analysis / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013820:Thermolysin / Q000737:chemistry / Q000378:metabolism
D006877:Hydroxamic Acids; D011480:Protease Inhibitors; D011506:Proteins; D045726:Metalloproteases; D013820:Thermolysin; C010531:actinonin