View source for 8juf


==Crystal structure of human MMP-7 in complex with inhibitor==
<StructureSection load='8juf' size='340' side='right'caption='[[8juf]], [[Resolution|resolution]] 1.39&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8juf]] is a 2 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=8JUF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JUF FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.39&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7SF:4-chloranyl-3-(trifluoromethyl)benzenesulfonic+acid'>7SF</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EOE:beta3-proline'>EOE</scene>, <scene name='pdbligand=GGL:GAMMA-L-GLUTAMIC+ACID'>GGL</scene>, <scene name='pdbligand=N9P:3-pyridin-4-yl-L-alanine'>N9P</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=TBG:3-METHYL-L-VALINE'>TBG</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=8juf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8juf OCA], [https://pdbe.org/8juf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8juf RCSB], [https://www.ebi.ac.uk/pdbsum/8juf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8juf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MMP7_HUMAN MMP7_HUMAN] Degrades casein, gelatins of types I, III, IV, and V, and fibronectin. Activates procollagenase.<ref>PMID:2550050</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Matrix metalloproteinase-7 (MMP-7) has been shown to play important roles in pathophysiological processes involved in the development/progression of diseases such as cancer and fibrosis. We discovered selective MMP-7 inhibitors composed of arylsulfonamide, carboxylate, and short peptides by a molecular hybridization approach. These compounds interacted with MMP-7 via multiple hydrogen bonds in the cocrystal structures. To obtain compounds for in vivo evaluation, we attempted structural optimization, particularly targeting Tyr167 at the S3 subsite through structure-based drug design, and identified compound 15 as showing improved MMP-7 potency and MMP subtype selectivity. A novel pi-pi stacking interaction with Tyr167 was achieved when 4-pyridylalanine was introduced as the P3 residue. Compound 15 suppressed the progression of kidney fibrosis in a dose-dependent manner in a mouse model of unilateral ureteral obstruction. Thus, we demonstrated, for the first time, that potent and selective MMP-7 inhibitors could prevent the progression of kidney fibrosis.

Structure-Based Optimization and Biological Evaluation of Potent and Selective MMP-7 Inhibitors for Kidney Fibrosis.,Abe-Sato K, Tabuse H, Kanazawa H, Kamitani M, Endo M, Tokura S, Wakabayashi S, Yahara T, Takeda T, Hitaka K, Gunji E, Kojima N, Oka Y J Med Chem. 2023 Oct 20. doi: 10.1021/acs.jmedchem.3c01166. PMID:37861435<ref>PMID:37861435</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8juf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Abe-Sato K]]
[[Category: Kamitani M]]
[[Category: Oka Y]]