2hu6: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor== | ==Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor== | ||
<StructureSection load='2hu6' size='340' side='right' caption='[[2hu6]], [[Resolution|resolution]] 1.32Å' scene=''> | <StructureSection load='2hu6' size='340' side='right' caption='[[2hu6]], [[Resolution|resolution]] 1.32Å' scene=''> | ||
| Line 7: | Line 8: | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMP12, HME ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMP12, HME ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Macrophage_elastase Macrophage elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.65 3.4.24.65] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Macrophage_elastase Macrophage elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.65 3.4.24.65] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hu6 OCA], [http://pdbe.org/2hu6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hu6 RCSB], [http://www.ebi.ac.uk/pdbsum/2hu6 PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hu6 OCA], [http://pdbe.org/2hu6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hu6 RCSB], [http://www.ebi.ac.uk/pdbsum/2hu6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2hu6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| Line 30: | Line 31: | ||
</div> | </div> | ||
<div class="pdbe-citations 2hu6" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 2hu6" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 11:16, 18 October 2017
Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitorCrystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor
Structural highlights
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 PubMedStarting 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||||||