Nature Structural Biology
1, 119 - 123 (1994)
doi:10.1038/nsb0294-119
Structure of human neutrophil collagenase reveals large S1' specificity pocketTravis Stams1, John C. Spurlino1, Douglas L. Smith1, Robert C. Wahl1, Thau F. Ho1, M. Walid Qoronfleh1, Tracey M. Banks1
& Byron Rubin1
1Sterling Winthrop Pharmaceutical Research Division, Collegeville, Pennsylvania 19426, USA 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.
REFERENCES
- Birkedal-Hansen, H. et al. Matrix metalloproteinases: a review. Crit. Rev. Oral Biol. Med. 4, 197−250 (1993). | PubMed | ChemPort |
- Mallaya, S.K. et al. Characterization of 58-kilodalton human neutrophil collagenase: comparison with human fibroblast enzyme. Biochemistry 29, 10628−10634 (1990). | PubMed |
- VanWart, H.E. Human neutrophil collagenase. Matrix supplement 1, 31−36 (1992). | ChemPort |
- 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). | PubMed | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- Schwartz, M.A. et al. Inhibition of human collagenases by sulfur-based substrate analogs. Biochem. biophys. Res. Comm. 176, 173−179 (1991). | PubMed | ISI | ChemPort |
- Mooktiar, K.A., Marlowe, C.K., Bartlett, P.A. & VanWart, H.E. Phosphonamidate inhibitors of human neutrophil collagenase. Biochemistry 26, 1962−1965 (1987). | PubMed |
- Schechter, I. & Berger, A. On the size of the active site proteases. Biochem. biophys. Res. Comm. 27, 157−162 (1967). | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- 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). | Article | ISI | ChemPort |
- Rossman, M.G. & Argos, R.J. Exploring structural homology of proteins. J. molec. Biol. 105, 75−96 (1976). | PubMed | ISI | ChemPort |
- Ponder, J.W. & Richards, F.M. Tertiary templates for proteins. J. molec. Biol. 193, 775−791 (1987). | PubMed | ISI | ChemPort |
- Murphy, G.J.P., Murphy, G., & Reynolds, J.J. The origin of matrix metalloproteinases and their familial relationships. FEBS Lett. 289, 4−7 (1991). | Article | PubMed | ISI | ChemPort |
- 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). | Article | ISI | ChemPort |
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