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. © 2005 Elsevier Ltd. All rights reserved.
N-Hydroxyurea as zinc binding group in matrix metalloproteinase inhibition: Mode of binding in a complex with MMP-8 / Cristina, Campestre; Mariangela, Agamennone; Paolo, Tortorella; Serena, Preziuso; Alessandro, Biasone; Enrico, Gavuzzo; Giorgio, Pochetti; Fernando, Mazza; Oliver, Hiller; Harald, Tschesche; Consalvi, Valerio; Carlo, Gallina. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 16:1(2006), pp. 20-24. [10.1016/j.bmcl.2005.09.057]
N-Hydroxyurea as zinc binding group in matrix metalloproteinase inhibition: Mode of binding in a complex with MMP-8
CONSALVI, Valerio;
2006
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. © 2005 Elsevier Ltd. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
