title: N-Hydroxyurea as zinc binding group in matrix metalloproteinase inhibition: mode of binding in a complex with MMP-8.
abstract: The first crystallographic structure of an N-hydroxyurea inhibitor bound into the active site of a matrix metalloproteinase is reported. The ligand and three other analogues were prepared and studied as inhibitors of MMP-2, MMP-3, and MMP-8. The crystal structure of the complex with MMP-8 shows that the N-hydroxyurea, contrary to the analogous hydroxamate, binds the catalytic zinc ion in a monodentate rather than bidentate mode and with high out-of-plane distortion of the amide bonds.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università degli Studi 'G. d'Annunzio', Chieti, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Campestre
authors.forename: Mariangela
authors.initials: M
authors.lastname: Agamennone
authors.forename: Paolo
authors.initials: P
authors.lastname: Tortorella
authors.forename: Serena
authors.initials: S
authors.lastname: Preziuso
authors.forename: Alessandro
authors.initials: A
authors.lastname: Biasone
authors.forename: Enrico
authors.initials: E
authors.lastname: Gavuzzo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pochetti
authors.forename: Fernando
authors.initials: F
authors.lastname: Mazza
authors.forename: Oliver
authors.initials: O
authors.lastname: Hiller
authors.forename: Harald
authors.initials: H
authors.lastname: Tschesche
authors.forename: Valerio
authors.initials: V
authors.lastname: Consalvi
authors.forename: Carlo
authors.initials: C
authors.lastname: Gallina
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006918:Hydroxyurea / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry; D019278:Matrix Metalloproteinase 3 / Q000737:chemistry; D020784:Matrix Metalloproteinase 8 / Q000737:chemistry* / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008956:Models, Chemical; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D013876:Thiophenes / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D015032:Zinc; D010100:Oxygen; D006918:Hydroxyurea