| Structural highlights
5i43 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| Related: | 5i3m, 5i2z, 5iol, 5i12 |
| Gene: | MMP12, HME (HUMAN) |
| Activity: | Macrophage elastase, with EC number 3.4.24.65 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[MMP12_HUMAN] May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.
Publication Abstract from PubMed
Matrix metalloproteinase-12 (MMP-12) can be considered an attractive target to study selective inhibitors useful in the development of new therapies for lung and cardiovascular diseases. In this study, a new series of arylsulfonamide carboxylates, with increased hydrophilicity resulting from conjugation with a beta-N-acetyl-d-glucosamine moiety, were designed and synthesized as MMP-12 selective inhibitors. Their inhibitory activity was evaluated on human MMPs by using the fluorimetric assay, and a crystallographic analysis was performed to characterize their binding mode. Among these glycoconjugates, a nanomolar MMP-12 inhibitor with improved water solubility, compound 3 [(R)-2-(N-(2-(3-(2-acetamido-2-deoxy-beta-d-glucopyranosyl)thioureido)ethyl)biphe nyl-4-ylsulfonamido)-3-methylbutanoic acid], was identified.
Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors.,Nuti E, Cuffaro D, D'Andrea F, Rosalia L, Tepshi L, Fabbi M, Carbotti G, Ferrini S, Santamaria S, Camodeca C, Ciccone L, Orlandini E, Nencetti S, Stura EA, Dive V, Rossello A ChemMedChem. 2016 Jun 30. doi: 10.1002/cmdc.201600235. PMID:27356908[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nuti E, Cuffaro D, D'Andrea F, Rosalia L, Tepshi L, Fabbi M, Carbotti G, Ferrini S, Santamaria S, Camodeca C, Ciccone L, Orlandini E, Nencetti S, Stura EA, Dive V, Rossello A. Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors. ChemMedChem. 2016 Jun 30. doi: 10.1002/cmdc.201600235. PMID:27356908 doi:http://dx.doi.org/10.1002/cmdc.201600235
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