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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Crystallography, X-Ray
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Enzyme Inhibitors / pharmacology*
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Escherichia coli / metabolism
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Humans
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Hydrogen-Ion Concentration
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Hydroxyurea / chemistry*
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Inhibitory Concentration 50
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Matrix Metalloproteinase 2 / chemistry
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Matrix Metalloproteinase 3 / chemistry
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Matrix Metalloproteinase 8 / chemistry*
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Matrix Metalloproteinase 8 / metabolism
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Matrix Metalloproteinase Inhibitors*
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Models, Chemical
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Models, Molecular
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Oxygen / chemistry
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Phenylalanine / analogs & derivatives
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Phenylalanine / chemistry
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Protein Binding
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Protein Conformation
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Thiophenes / chemistry
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Zinc / chemistry*
Substances
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Enzyme Inhibitors
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Matrix Metalloproteinase Inhibitors
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Thiophenes
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Phenylalanine
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batimastat
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Matrix Metalloproteinase 3
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 8
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Zinc
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Oxygen
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Hydroxyurea