The crystal structure of the catalytic domain of human neutrophil collagenase complexed with a peptide transition state analogue has been determined to a resolution of 2.1 Å. The structure of the neutrophil enzyme, when compared with the three dimensional structure of the corresponding human f ibroblast collagenase, shows differences in the first, S1′, of the three enzyme specificity subsites on the carboxy–terminal side of the substrate scissile bond. The S1′ pocket in the neutrophil collagenase is significantly larger than the equivalent site in the f ibroblast enzyme, suggesting that the former enzyme has a broader range of possible substrates. Such differences also suggest approaches for the design of selective matrix metalloproteinase inhibitors.
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Birkedal-Hansen, H. et al. Matrix metalloproteinases: a review. Crit. Rev. Oral Biol. Med. 4, 197–250 (1993).
Mallaya, S.K. et al. Characterization of 58-kilodalton human neutrophil collagenase: comparison with human fibroblast enzyme. Biochemistry 29, 10628–10634 (1990).
VanWart, H.E. Human neutrophil collagenase. Matrix supplement 1, 31–36 (1992).
Netzel-Arnett, S., Fields, G., Birkedal-Hanson, H. & VanWart, H.E. Sequence specificities of human fibroblast and human neutrophil collagenase. J. biol. Chem. 266, 6747–6755 (1991).
Hasty, K.A., Jeffrey, J.J., Hibbs, M.S. & Welgus, H.G. The collagen substrate specificity of human neutrophil collagenase. J. biol. Chem. 262, 10048–10052 (1987).
Schwartz, M.A. et al. Inhibition of human collagenases by sulfur-based substrate analogs. Biochem. biophys. Res. Comm. 176, 173–179 (1991).
Mooktiar, K.A., Marlowe, C.K., Bartlett, P.A. & VanWart, H.E. Phosphonamidate inhibitors of human neutrophil collagenase. Biochemistry 26, 1962–1965 (1987).
Schechter, I. & Berger, A. On the size of the active site proteases. Biochem. biophys. Res. Comm. 27, 157–162 (1967).
Hasty, K.A. et al. Human neutrophil collagenase a distant gene product with homology to other matrix metalloproteinases. J. biol. Chem. 265, 11421–11424 (1990).
Devarajan, P., Mooktiar, K.A., VanWart, H.E. & Berliner, N. Structure and expression of the cDNA encoding human neutrophil collagenase. Blood 77, 2731–2738 (1991).
Ho, T.F. et al. Gene expression,purification and characterization of recombinant human neutrophil collagenase. Gene (in the press).
Spurlino, J.C. et al. 1.56 Å structure of mature truncated human fibroblast collagenase. Proteins (in the press).
Fitzgerald, P.M.D. MERLOT, an intergrated package of computer programs for the determination of crystal structures by molecular replacement. J. appl. Crystallogr. 21, 273–278 (1988).
Rossman, M.G. & Argos, R.J. Exploring structural homology of proteins. J. molec. Biol. 105, 75–96 (1976).
Ponder, J.W. & Richards, F.M. Tertiary templates for proteins. J. molec. Biol. 193, 775–791 (1987).
Murphy, G.J.P., Murphy, G., & Reynolds, J.J. The origin of matrix metalloproteinases and their familial relationships. FEBS Lett. 289, 4–7 (1991).
Leslie, A.G.W. Recent changes to the MOSFLM package for processing film and image plate data. CCP4 and ESF-EACMB Newsletter on Protein Crystallography 26, (1992).
Sack, J.S. CHAIN — A crystallographic modelling program.J. molec. Graph. 6, 244–245 (1988).
Brunger, A.T. XPLOR Version 3.1 A System for X-ray Crystallography and NMR (Yale University Press, New Haven and London, 1992).
Hendrickson, W.A. & Konnert, J.H. in: Biomolecular Structure, Function, Conformation, and Evolution (ed. Srinivasan, R.) 43–57 (Pergamon, Oxford, 1980) .
Carson, M. Ribbon models of macromolecules. J. molec. Graph. 5, 103–106 (1987).
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Stams, T., Spurlino, J., Smith, D. et al. Structure of human neutrophil collagenase reveals large S1′ specificity pocket. Nat Struct Mol Biol 1, 119–123 (1994). https://doi.org/10.1038/nsb0294-119
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