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4EFS

Human MMP12 in complex with L-glutamate motif inhibitor

Summary for 4EFS
Entry DOI10.2210/pdb4efs/pdb
Related3LIK 3LIL 3LIR 3LJG 3TS4
DescriptorMacrophage metalloelastase, ZINC ION, CALCIUM ION, ... (10 entities in total)
Functional Keywordspseudo peptides, potent inhibitors, metzincin, zinc protease, l-glutamate motif inhibitors, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
Biological sourceHomo sapiens (human)
Cellular locationSecreted, extracellular space, extracellular matrix (Probable): P39900
Total number of polymer chains1
Total formula weight18864.88
Authors
Stura, E.A.,Dive, V.,Devel, L.,Czarny, B.,Beau, F.,Vera, L. (deposition date: 2012-03-30, release date: 2012-06-20, Last modification date: 2023-09-13)
Primary citationDevel, L.,Beau, F.,Amoura, M.,Vera, L.,Cassar-Lajeunesse, E.,Garcia, S.,Czarny, B.,Stura, E.A.,Dive, V.
Simple pseudo-dipeptides with a P2' glutamate: a novel inhibitor family of matrix metalloproteases and other metzincins.
J.Biol.Chem., 287:26647-26656, 2012
Cited by
PubMed Abstract: A series of pseudo-peptides with general formula X-l-Glu-NH(2) (with X corresponding to an acyl moiety with a long aryl-alkyl side chain) have been synthesized, evaluated as inhibitors of matrix metalloproteases (MMPs), and found to display remarkable nanomolar affinity. The loss in potency associated with a substitution of the P(2)' l-glutamate by a l-glutamine corroborates the importance of a carboxylate at this position. The binding mode of some of these inhibitors was characterized in solution and by x-ray crystallography in complex with various MMPs. The x-ray crystal structures reveal an unusual binding mode with the glutamate side chain chelating the active site zinc ion. Competition experiments between these inhibitors and acetohydroxamic acid, a small zinc-binding molecule, are in accord with the crystallographic results. One of these pseudo-dipeptides displays potency and selectivity toward MMP-12 similar to the best MMP-12 inhibitors reported to date. This novel family of pseudo peptides opens new opportunities to develop potent and selective inhibitors for several metzincins.
PubMed: 22689580
DOI: 10.1074/jbc.M112.380782
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.63 Å)
Structure validation

227561

數據於2024-11-20公開中

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