N-Hydroxyurea as zinc binding group in matrix metalloproteinase inhibition: mode of binding in a complex with MMP-8.

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Campestre C, Agamennone M, Tortorella P, Preziuso S, Biasone A, Gavuzzo E, Pochetti G, Mazza F, Hiller O, Tschesche H, Consalvi V, Gallina C

N-Hydroxyurea as zinc binding group in matrix metalloproteinase inhibition: mode of binding in a complex with MMP-8.

Bioorg Med Chem Lett. 2006 Jan 1;16(1):20-4. Epub 2005 Oct 18.

PubMed ID

16242329 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
N-{2-[(4'-CYANO-1,1'-BIPHENYL-4-YL)OXY]ETHYL}-N'-HYDROXY-N-METHYLUREA	Neutrophil collagenase	IC 50 (nM)	1200000	N/A	N/A	Details