3TS4
Human MMP12 in complex with L-glutamate motif inhibitor
Summary for 3TS4
| Entry DOI | 10.2210/pdb3ts4/pdb |
| Related | 3LIK 3LIL 3LIR 3LJG 3TSK 3TT4 3TVC |
| Related PRD ID | PRD_001058 |
| Descriptor | Macrophage metalloelastase, ZINC ION, CALCIUM ION, ... (7 entities in total) |
| Functional Keywords | pseudo dipeptides, potent inhibitors, metzincin, zinc protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Secreted, extracellular space, extracellular matrix (Probable): P39900 |
| Total number of polymer chains | 1 |
| Total formula weight | 18593.54 |
| Authors | Stura, E.A.,Dive, V.,Devel, L.,Czarny, B.,Beau, F.,Vera, L. (deposition date: 2011-09-12, release date: 2012-06-20, Last modification date: 2023-09-13) |
| Primary citation | Devel, 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: 22689580DOI: 10.1074/jbc.M112.380782 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.587 Å) |
Structure validation
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