4gr8
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4gr8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GR8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GR8 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4gr8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GR8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GR8 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=R4C:N-{(2S)-3-[(R)-(4-BROMOPHENYL)(HYDROXY)PHOSPHORYL]-2-[(3-PHENYL-1,2-OXAZOL-5-YL)METHYL]PROPANOYL}-L-ALANYL-L-ALANINAMIDE'>R4C</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.299Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=R4C:N-{(2S)-3-[(R)-(4-BROMOPHENYL)(HYDROXY)PHOSPHORYL]-2-[(3-PHENYL-1,2-OXAZOL-5-YL)METHYL]PROPANOYL}-L-ALANYL-L-ALANINAMIDE'>R4C</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4gr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gr8 OCA], [https://pdbe.org/4gr8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gr8 RCSB], [https://www.ebi.ac.uk/pdbsum/4gr8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gr8 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4gr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gr8 OCA], [https://pdbe.org/4gr8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gr8 RCSB], [https://www.ebi.ac.uk/pdbsum/4gr8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gr8 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/MMP12_HUMAN 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. | [https://www.uniprot.org/uniprot/MMP12_HUMAN 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. | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | The molecular determinants responsible for the potency of the RXP470.1 phosphinic peptide inhibitor towards matrix metalloprotease-12 (MMP-12) remain elusive. To address this issue, structure-activity study, X-ray crystallography and isothermal titration calorimetry (ITC) experiments were performed. The crystal structure of MMP-12/inhibitor complex (1.15 A) reveals that the inhibitor establishes multiple interactions with the MMP-12 active site, with its long P1' side chain filling most part of the S1' deep cavity. ITC experiments indicate that the binding of this inhibitor to MMP-12 is mostly entropy driven (DeltaG degrees = -13.1 kcal/mol, DeltaH degrees = -2.53 kcal/mol and -TDeltaS degrees = -10.60 kcal/mol) and involves a proton uptake from the buffer. Comparing phosphinic versus hydroxamate inhibitors reveals that the chelation of the zinc ion is slightly different, leading the inhibitor backbone to adopt a position in which the hydrogen bonding with the MMP-12 active site is less favorable in phosphinic inhibitor, while maintaining high affinity. | ||
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| - | Molecular determinants of a selective matrix metalloprotease-12 inhibitor: Insights from crystallography and thermodynamic studies.,Czarny B, Stura EA, Devel L, Vera L, Lajeunesse E, Beau F, Calderone V, Fragai M, Luchinat C, Dive V J Med Chem. 2013 Jan 23. PMID:23343195<ref>PMID:23343195</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4gr8" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]] | *[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of the catalytic domain of Human MMP12 in complex with selective phosphinic inhibitor RXP470C
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Categories: Homo sapiens | Large Structures | Beau F | Cassar-Lajeunesse E | Devel L | Dive V | Stura EA | Vera L
