title: Structure of human neutrophil collagenase reveals large S1' specificity pocket.
abstract: 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 A. The structure of the neutrophil enzyme, when compared with the three dimensional structure of the corresponding human fibroblast 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 fibroblast 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.
authors.affiliation: Sterling Winthrop Pharmaceuticals Research Division, Collegeville, Pennsylvania 19426, USA.
authors.forename: T
authors.initials: T
authors.lastname: Stams
authors.forename: J C
authors.initials: JC
authors.lastname: Spurlino
authors.forename: D L
authors.initials: DL
authors.lastname: Smith
authors.forename: R C
authors.initials: RC
authors.lastname: Wahl
authors.forename: T F
authors.initials: TF
authors.lastname: Ho
authors.forename: M W
authors.initials: MW
authors.lastname: Qoronfleh
authors.forename: T M
authors.initials: TM
authors.lastname: Banks
authors.forename: B
authors.initials: B
authors.lastname: Rubin
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D017364:Collagenases / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D066298:In Vitro Techniques; D061965:Matrix Metalloproteinase Inhibitors; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009504:Neutrophils / Q000201:enzymology*; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D017364:Collagenases