5i2z

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==Crystal structure of the catalytic domain of MMP-12 in complex with a selective sugar-conjugated triazole-linked carboxylate chelating water-soluble inhibitor (DC24).==
==Crystal structure of the catalytic domain of MMP-12 in complex with a selective sugar-conjugated triazole-linked carboxylate chelating water-soluble inhibitor (DC24).==
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<StructureSection load='5i2z' size='340' side='right' caption='[[5i2z]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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<StructureSection load='5i2z' size='340' side='right'caption='[[5i2z]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5i2z]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I2Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I2Z FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5i2z]] is a 4 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=5I2Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I2Z FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene>, <scene name='pdbligand=V24:N-[([1,1-BIPHENYL]-4-YL)SULFONYL]-N-({1-[3,4,6-TRI-O-ACETYL-2-(ACETYLAMINO)-2-DEOXY-BETA-D-GLUCOPYRANOSYL]-1H-1,2,3-TRIAZOL-4-YL}METHYL)-D-VALINE'>V24</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5iol|5iol]], [[5i12|5i12]]</td></tr>
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<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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</scene>, <scene name='pdbligand=V24:N-[([1,1-BIPHENYL]-4-YL)SULFONYL]-N-({1-[3,4,6-TRI-O-ACETYL-2-(ACETYLAMINO)-2-DEOXY-BETA-D-GLUCOPYRANOSYL]-1H-1,2,3-TRIAZOL-4-YL}METHYL)-D-VALINE'>V24</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5i2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i2z OCA], [https://pdbe.org/5i2z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i2z RCSB], [https://www.ebi.ac.uk/pdbsum/5i2z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i2z ProSAT]</span></td></tr>
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<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=5i2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i2z OCA], [http://pdbe.org/5i2z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i2z RCSB], [http://www.ebi.ac.uk/pdbsum/5i2z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i2z ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://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.
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[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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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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<ref>PMID:27356908</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5i2z" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Macrophage elastase]]
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[[Category: Homo sapiens]]
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[[Category: Ciccone, L]]
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[[Category: Large Structures]]
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[[Category: Cuffaro, D]]
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[[Category: Ciccone L]]
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[[Category: Rosalia, L]]
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[[Category: Cuffaro D]]
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[[Category: Rossello, A]]
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[[Category: Rosalia L]]
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[[Category: Stura, E A]]
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[[Category: Rossello A]]
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[[Category: Tepshi, L]]
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[[Category: Stura EA]]
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[[Category: Complex]]
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[[Category: Tepshi L]]
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[[Category: Glycoconjugate]]
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[[Category: Hydrolase]]
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[[Category: Inhibitor]]
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[[Category: Metalloprotease]]
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Current revision

Crystal structure of the catalytic domain of MMP-12 in complex with a selective sugar-conjugated triazole-linked carboxylate chelating water-soluble inhibitor (DC24).

PDB ID 5i2z

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