2hu6

Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor

spinqualitylabelsall models 2hu6, resolution 1.32Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2hu6 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.32Å Ligands: 37A, CA, HAE, ZN 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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Starting from 3-aza-6,8-dioxa-bicyclo[3.2.1]octane scaffold (BTAa) a virtual library of molecules was generated and screened in silico against the crystal structure of the Human Macrophage Metalloelastase (MMP-12). The molecules obtaining high score were synthesized and the affinity for the catalytic domain of MMP-12 was experimentally proved by NMR experiments. A BTAa scaffold 20 having a N-hydroxyurea group in position 3 and a p-phenylbenzylcarboxy amide in position 7 showed a fair inhibition potency (IC50 = 149 microM) for MMP-12 and some selectivity towards five different MMPs. These results, taken together with the X-ray structure of the adduct between MMP-12, the inhibitor 20 and the acetohydroxamic acid (AHA), suggest that bicyclic scaffold derivatives may be exploited for the design of new selective matrix metalloproteinase inhibitors (MMPIs). Synthesis of bicyclic molecular scaffolds (BTAa): an investigation towards new selective MMP-12 inhibitors.,Mannino C, Nievo M, Machetti F, Papakyriakou A, Calderone V, Fragai M, Guarna A Bioorg Med Chem. 2006 Nov 15;14(22):7392-403. Epub 2006 Aug 8. PMID:16899369 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Matrix metalloproteinase 3D structures

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