1xuc
From Proteopedia
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| , resolution 1.700Å | |||||||
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| Ligands: | , and | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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