[Natural inhibitor of metalloproteinases: structural and functional study].
A potent collagenase inhibitor was purified from cells of calf aorta medial tissue maintained in culture. This molecule was characterized and identified as TIMP (Tissue Inhibitor of Metalloproteinases). Formation of a TIMP--collagenase complex was demonstrated chromatographically using pure TIMP and pure pig synovial cell collagenase. The N-terminal aminoacid sequence of TIMP was determined and, using appropriate oligonucleotide probes the human genes was cloned from a human cDNA bank. This gene was expressed in E. coli, and fully active TIMP was obtained after a denaturation renaturation process. The interest of TIMP as a model for the design of novel collagenase inhibitors is discussed.
Faucher
D
D
Rhône-Poulenc Santé (CRMA), Site de Recherche de Monts, France.
Lelièvre
Y
Y
Boiziau
J
J
Cornet
P
P
Cartwright
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000032:analysis; D002417:Cattle; D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011489:Protein Denaturation; D011994:Recombinant Proteins; D013552:Swine; D013583:Synovial Membrane / Q000201:enzymology; D019714:Tissue Inhibitor of Metalloproteinases
D004791:Enzyme Inhibitors; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D008666:Metalloendopeptidases; D003012:Microbial Collagenase
Inhibiteur naturel des métalloprotéinases: étude structurale et fonctionnelle.