title: Matrix metalloproteinase-inhibitor interaction: the solution structure of the catalytic domain of human matrix metalloproteinase-3 with different inhibitors.
abstract: We structurally characterized the adducts of the catalytic domain of matrix metalloproteinase-3 (MMP3) with three different nonpeptidic inhibitors by solving the solution structure of one adduct [MMP3-N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid] and then by calculating structural models of the other two adducts using a reduced set of experimental NMR data, following a recently proposed procedure (Bertini et al. in J. Med. Chem. 48:7544-7559, 2005). The inhibitors were selected with the criteria of maintaining in all of them the same zinc-coordinating moiety and of selectively changing the substituents and/or the functional groups. The backbone dynamics on various time scales have been characterized as well. The comparison among these structures and with others previously reported allowed us to elucidate fine details of inhibitor-receptor interactions and to develop some criteria, which could guide in optimizing the design of selective inhibitors.
authors: Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, Sesto Fiorentino, Italy.
authors: Luis A
authors: LA
authors: Alcaraz
authors: Lucia
authors: L
authors: Banci
authors: Ivano
authors: I
authors: Bertini
authors: Francesca
authors: F
authors: Cantini
authors: Antonio
authors: A
authors: Donaire
authors: Leonardo
authors: L
authors: Gonnelli
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry; D019278:Matrix Metalloproteinase 3 / Q000737:chemistry*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012996:Solutions; D013449:Sulfonamides / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C500716:N-isobutyl-N-(4-methoxyphenylsulfonyl)glycylhydroxamic acid; D012996:Solutions; D013449:Sulfonamides; D019278:Matrix Metalloproteinase 3
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