7xjo: Difference between revisions

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 <StructureSection load='7xjo' size='340' side='right'caption='[[7xjo]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7xjo]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XJO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XJO FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7xjo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XJO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XJO FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DAB:2,4-DIAMINOBUTYRIC+ACID'>DAB</scene>, <scene name='pdbligand=H7I:(4~{S})-5-[(2~{S})-2-(2-azanyl-2-oxidanylidene-ethyl)pyrrolidin-1-yl]-4-(methylamino)-5-oxidanylidene-pentanoic+acid'>H7I</scene>, <scene name='pdbligand=LEA:PENTANOIC+ACID'>LEA</scene>, <scene name='pdbligand=OUL:4-(4-aminocarbonylphenoxy)benzamide'>OUL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAB:2,4-DIAMINOBUTYRIC+ACID'>DAB</scene>, <scene name='pdbligand=H7I:'>H7I</scene>, <scene name='pdbligand=LEA:PENTANOIC+ACID'>LEA</scene>, <scene name='pdbligand=OUL:'>OUL</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Gelatinase_A Gelatinase A], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.24 3.4.24.24] </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=7xjo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xjo OCA], [https://pdbe.org/7xjo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xjo RCSB], [https://www.ebi.ac.uk/pdbsum/7xjo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xjo ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Matrix metalloproteinase-2 (MMP2) is a zinc-dependent endopeptidase that plays important roles in the degradation of extracellular matrix proteins. MMP2 is considered to be an attractive target for the treatment of various diseases such as cancer, arthritis, and fibrosis. In this study, we have developed a novel class of MMP2-selective inhibitors by hybridizing the peptide that binds to a zinc ion and S2-S5 pockets with small molecules that bind to the S1' pocket. Structural modifications based on X-ray crystallography revealed that the introduction of 2,4-diaminobutanoic acid (Dab) at position 4 dramatically enhanced MMP2 selectivity by forming an electrostatic interaction with Glu130. After improving the metabolic and chemical stability, TP0556351 (9) was identified. It exhibited potent MMP2 inhibitory activity (IC50 = 0.20 nM) and extremely high selectivity. It suppressed the accumulation of collagen in a bleomycin-induced idiopathic pulmonary fibrosis model in mice, demonstrating the efficacy of MMP2-selective inhibitors for fibrosis.
-Discovery of Aryloxyphenyl-Heptapeptide Hybrids as Potent and Selective Matrix Metalloproteinase-2 Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis.,Takeuchi T, Hayashi M, Tamita T, Nomura Y, Kojima N, Mitani A, Takeda T, Hitaka K, Kato Y, Kamitani M, Mima M, Toki H, Ohkubo M, Nozoe A, Kakinuma H J Med Chem. 2022 Jun 23;65(12):8493-8510. doi: 10.1021/acs.jmedchem.2c00613. Epub, 2022 Jun 10. PMID:35687819<ref>PMID:35687819</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 7xjo" style="background-color:#fffaf0;"></div>
-== References ==
-<references/>
 __TOC__
 </StructureSection>
-[[Category: Gelatinase A]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Kamitani, M]]
+[[Category: Synthetic construct]]
-[[Category: Mima, M]]
+[[Category: Kamitani M]]
-[[Category: Takeuchi, T]]
+[[Category: Mima M]]
-[[Category: 72 kda type iv collagenase]]
+[[Category: Takeuchi T]]
-[[Category: Gelatinase some]]
-[[Category: Hydrolase]]
-[[Category: Matrix metalloproteinase-2]]