1xuc
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(New page: 200px<br /> <applet load="1xuc" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xuc, resolution 1.700Å" /> '''Matrix metalloprot...)
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Revision as of 18:04, 12 November 2007
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Matrix metalloproteinase-13 complexed with non-zinc binding inhibitor
Overview
Inhibitors for matrix metalloproteinases (MMPs) are under investigation, for the treatment of cancer, arthritis, and cardiovascular disease. Here, we report a class of highly selective MMP-13 inhibitors (pyrimidine, dicarboxamides) that exhibit no detectable activity against other MMPs., The high-resolution X-ray structures of three molecules of this series, bound to MMP-13 reveal a novel binding mode characterized by the absence, of interactions between the inhibitors and the catalytic zinc. The, inhibitors bind in the S1' pocket and extend into an additional S1' side, pocket, which is unique to MMP-13. We analyze the determinants for, selectivity and describe the rational design of improved compounds with, low nanomolar affinity.
About this Structure
1XUC is a Single protein structure of sequence from Homo sapiens with ZN, CA and PB3 as ligands. Full crystallographic information is available from OCA.
Reference
Structural basis for the highly selective inhibition of MMP-13., Engel CK, Pirard B, Schimanski S, Kirsch R, Habermann J, Klingler O, Schlotte V, Weithmann KU, Wendt KU, Chem Biol. 2005 Feb;12(2):181-9. PMID:15734645
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