1xuc: Difference between revisions

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==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.

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==

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[[Category: Homo sapiens]]

[[Category: Single protein]]

[[Category: Engel, C.K.]]

[[Category: Engel, C K.]]

[[Category: Wendt, K.U.]]

[[Category: Wendt, K U.]]

[[Category: CA]]

[[Category: PB3]]

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[[Category: non-zinc binding inhibitor]]

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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:58:45 2008''

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@@ Line 4: / Line 4: @@
 ==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.
+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==
@@ Line 13: / Line 13: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Engel, C.K.]]
+[[Category: Engel, C K.]]
-[[Category: Wendt, K.U.]]
+[[Category: Wendt, K U.]]
 [[Category: CA]]
 [[Category: PB3]]
@@ Line 21: / Line 21: @@
 [[Category: non-zinc binding inhibitor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:10:29 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:58:45 2008''