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. © 2007 SBIC.
Matrix metalloproteinase-inhibitor interaction: the solution structure of the catalytic domain of human matrix metalloproteinase-3 with different inhibitors / L.A.Alcaraz;L.Banci;I.Bertini;F.Cantini;A.Donaire;L.Gonnelli. - In: JBIC. - ISSN 0949-8257. - STAMPA. - 12:(2007), pp. 1197-1206. [10.1007/s00775-007-0288-9]