Collagen/collagenase interaction: Does the enzyme mimic the conformation of its own substrate?

In this report, we present a hypothesis on the mechanism used by interstitial collagenases to cleave their natural substrate, interstitial collagens. The hypothesis is based on the assumption that the proline hinge domain of interstitial collagenase adopts a collagen‐like conformation. With a colla‐ gen‐like domain, the enzyme is able to disturb the quaternary organization of the triple helix in the collagenase‐susceptible site. A modeling analysis suggests that interaction between prolines of both collagen and collagenase forming a kind of “proline zipper” is involved in the destabilization step. This destabilization makes the three‐collagen helix susceptible to the catalytic cleft of the catalytic core.—de Souza, S. J., Pereira, H. M., Jacchieri, S., Brentani, R. R. Collagen/collagenase interaction: Does the enzyme mimic the conformation of its own substrate? FASEB J. 10, 927‐930 (1996)

[1]  T. Pourmotabbed,et al.  Structure-function relationship of human neutrophil collagenase: identification of regions responsible for substrate specificity and general proteinase activity. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[2]  James P. Quigley,et al.  Matrix Metalloproteinase-2 Is an Interstitial Collagenase , 1995, The Journal of Biological Chemistry.

[3]  Y. DeClerck,et al.  Fragmentation of human polymorphonuclear-leucocyte collagenase. , 1993, The Biochemical journal.

[4]  R. Brentani,et al.  Collagen binding site in collagenase can be determined using the concept of sense-antisense peptide interactions. , 1992, The Journal of biological chemistry.

[5]  C. Turck,et al.  The substrate specificity of Uca pugilator collagenolytic serine protease 1 correlates with the bovine type I collagen cleavage sites. , 1994, The Journal of biological chemistry.

[6]  H. Tschesche,et al.  The recombinant catalytic domain of human neutrophil collagenase lacks type I collagen substrate specificity. , 1993, Biochemical and Biophysical Research Communications - BBRC.

[7]  M. Williamson,et al.  The structure and function of proline-rich regions in proteins. , 1994, The Biochemical journal.

[8]  T. Blundell,et al.  X-ray analysis (1. 4-A resolution) of avian pancreatic polypeptide: Small globular protein hormone. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[9]  I. Clark,et al.  Fragments of human fibroblast collagenase. Purification and characterization. , 1989, The Biochemical journal.

[10]  A M Hassell,et al.  Structure of the catalytic domain of fibroblast collagenase complexed with an inhibitor. , 1994, Science.

[11]  J. Woessner,et al.  Matrix metalloproteinases and their inhibitors in connective tissue remodeling , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[12]  C. Cambillau,et al.  Solution conformation of human neuropeptide Y by 1H nuclear magnetic resonance and restrained molecular dynamics. , 1992, European journal of biochemistry.

[13]  R. Huber,et al.  The X‐ray crystal structure of the catalytic domain of human neutrophil collagenase inhibited by a substrate analogue reveals the essentials for catalysis and specificity. , 1994, The EMBO journal.

[14]  N. Borkakoti,et al.  Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor , 1994, Nature Structural Biology.