7vm5: Difference between revisions

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-'''Unreleased structure'''
-The entry 7vm5 is ON HOLD
+==Crystal structure of uPA in complex with 4-guanidinobenzoic acid==
+<StructureSection load='7vm5' size='340' side='right'caption='[[7vm5]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7vm5]] 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=7VM5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VM5 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]] 1.97&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GBS:4-GUANIDINOBENZOIC+ACID'>GBS</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=7vm5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vm5 OCA], [https://pdbe.org/7vm5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vm5 RCSB], [https://www.ebi.ac.uk/pdbsum/7vm5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vm5 ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Nafamostat mesylate (NM) is a synthetic compound that inhibits various serine proteases produced during the coagulation cascade and inflammation. Previous studies showed that NM was a highly safe drug for the treatment of different cancers, but the precise functions and mechanisms of NM are not clear. In this study, we determined a series of crystal structures of NM and its hydrolysates in complex with a serine protease (urokinase-type plasminogen activator [uPA]). These structures reveal that NM was cleaved by uPA and that a hydrolyzed product (4-guanidinobenzoic acid [GBA]) remained covalently linked to Ser195 of uPA, and the other hydrolyzed product (6-amidino-2-naphthol [6A2N]) released from uPA. Strikingly, in the inactive uPA (uPA-S195A):NM structure, the 6A2N side of intact NM binds to the specific pocket of uPA. Molecular dynamics simulations and end-point binding free-energy calculations show that the conf1 of NM (6A2N as P1 group) in the uPA-S195A:NM complex may be more stable than conf2 of NM (GBA as P1 group). Moreover, in the structure of uPA:NM complex, the imidazole group of His57 flips further away from Ser195 and disrupts the stable canonical catalytic triad conformation. These results not only reveal the inhibitory mechanism of NM as an efficient serine protease inhibitor but also might provide the structural basis for the further development of serine protease inhibitors.
-Authors: Jiang, L.G., Huang, M.D.
+Structural study of the uPA-nafamostat complex reveals a covalent inhibitory mechanism of nafamostat.,Zhou Y, Wu J, Xue G, Li J, Jiang L, Huang M Biophys J. 2022 Oct 18;121(20):3940-3949. doi: 10.1016/j.bpj.2022.08.034. Epub , 2022 Aug 29. PMID:36039386<ref>PMID:36039386</ref>
-Description: Crystal structure of uPA in complex with 4-guanidinobenzoic acid
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Huang, M.D]]
+<div class="pdbe-citations 7vm5" style="background-color:#fffaf0;"></div>
-[[Category: Jiang, L.G]]
+==See Also==
+*[[Urokinase 3D Structures|Urokinase 3D Structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Huang MD]]
+[[Category: Jiang LG]]