Inhibition of collagenase by Cr(III): its relevance to stabilization of collagen

Bacterial collagenase has now been reacted with a select series of Cr(III) complexes and modifications in the activity of chromium-modified collagenas e has been deduced from the extent of hydrolysis of (2-furanacryloyl-L-leuc yl-glycyl-L-proly-L-alanine), FALGPA. A homologous series of Cr(III) comple xes with dimeric, trimeric and tetrameric structures as in (1) under bar, ( 2) under bar and (3) under bar respectively has been investigated for their ability to inhibit the action of collagenase against FALGPA. Whereas compe titive and non-competitive modes of inhibition of collagenase are expressed by (1) under bar, (dimer) and (2) under bar, (trimer) respectively, the te tramer, (3) under bar, exhibits poor affinity to collagenase and the inhibi tion of the enzyme activity is uncompetitive. Evidence for different modes of inhibition of collagenase depending on the nature of Cr(III) species has been presented in this work. Circular dichroism and gel electrophoresis da ta on Cr(III) modified collagenase corroborate the hypothesis that the inhi bition of collagenase by the heavy metal ion arises from secondary and quat ernary structural changes in the enzyme. The implications of the observed C r(III) species specific inhibition of collagenase in gaining new insight in to the mechanism of stabilization of collagen by Cr(III) are discussed. (C) 2000 Elsevier Science B.V. All rights reserved.