6shh
From Proteopedia
(Difference between revisions)
| (2 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
==Human kallikrein 7 with aromatic coumarinic ester compound 1 covalently bound to H57== | ==Human kallikrein 7 with aromatic coumarinic ester compound 1 covalently bound to H57== | ||
| - | <StructureSection load='6shh' size='340' side='right'caption='[[6shh]]' scene=''> | + | <StructureSection load='6shh' size='340' side='right'caption='[[6shh]], [[Resolution|resolution]] 2.00Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SHH OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SHH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SHH FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SH7:(3-chlorophenyl)+6-methyl-2-oxidanylidene-chromene-3-carboxylate'>SH7</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6shh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6shh OCA], [https://pdbe.org/6shh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6shh RCSB], [https://www.ebi.ac.uk/pdbsum/6shh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6shh ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The serine protease kallikrein-related peptidase 7 (KLK7) is a member of the human tissue kallikreins. Its dysregulation leads to pathophysiological inflammatory processes in the skin. Furthermore, it plays a role in several types of cancer. For the treatment of KLK7-associated diseases, coumarinic esters have been developed as small molecule enzyme inhibitors. To characterize the inhibition mode of these inhibitors, we analyzed structures of the inhibited protease by X-ray crystallography. Electron density shows the inhibitors covalently attached to His57 of the catalytic triad. This confirms the irreversible character of the inhibition process. Upon inhibitor binding His57 undergoes an outward rotation thus the catalytic triad of the protease is disrupted. Besides, the halophenyl moiety of the inhibitor was absent in the final enzyme-inhibitor complex due to hydrolysis of the ester linkage. With these results, we analyze the structural basis of KLK7 inhibition by covalent attachment of aromatic coumarinic esters. | ||
| + | |||
| + | Structural studies on the inhibitory binding mode of aromatic coumarinic esters to human kallikrein-related peptidase 7.,Hanke S, Tindall C, Pippel J, Ulbricht D, Pirotte B, Reboud-Ravaux M, Heiker JT, Strater N J Med Chem. 2020 May 6. doi: 10.1021/acs.jmedchem.9b01806. PMID:32374603<ref>PMID:32374603</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6shh" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Kallikrein 3D structures|Kallikrein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Human kallikrein 7 with aromatic coumarinic ester compound 1 covalently bound to H57
| |||||||||||
