4k1e
From Proteopedia
(Difference between revisions)
| Line 7: | Line 7: | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2bdg|2bdg]], [[2bdi|2bdi]], [[2bdh|2bdh]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2bdg|2bdg]], [[2bdi|2bdi]], [[2bdh|2bdh]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KLK4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KLK4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| - | <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=4k1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k1e OCA], [http://pdbe.org/4k1e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k1e RCSB], [http://www.ebi.ac.uk/pdbsum/4k1e PDBsum]</span></td></tr> | + | <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=4k1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k1e OCA], [http://pdbe.org/4k1e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k1e RCSB], [http://www.ebi.ac.uk/pdbsum/4k1e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k1e ProSAT]</span></td></tr> |
</table> | </table> | ||
== Disease == | == Disease == | ||
| Line 13: | Line 13: | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/KLK4_HUMAN KLK4_HUMAN]] Involved in enamel formation.<ref>PMID:15235027</ref> [[http://www.uniprot.org/uniprot/SFTI1_HELAN SFTI1_HELAN]] Inhibits trypsin, cathepsin G, elastase, chymotrypsin and thrombin. Does not inhibit factor Xa.<ref>PMID:10390350</ref> | [[http://www.uniprot.org/uniprot/KLK4_HUMAN KLK4_HUMAN]] Involved in enamel formation.<ref>PMID:15235027</ref> [[http://www.uniprot.org/uniprot/SFTI1_HELAN SFTI1_HELAN]] Inhibits trypsin, cathepsin G, elastase, chymotrypsin and thrombin. Does not inhibit factor Xa.<ref>PMID:10390350</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The kallikrein-related peptidase (KLK) family of proteases is involved in many aspects of human health and disease. One member of this family, KLK4, has been implicated in cancer development and metastasis. Understanding mechanisms of inactivation are critical to developing selective KLK4 inhibitors. We have determined the X-ray crystal structures of KLK4 in complex with both sunflower trypsin inhibitor-1 (SFTI-1) and a rationally designed SFTI-1 derivative to atomic (~1 A) resolution, as well as with bound nickel. These structures offer a structural rationalization for the potency and selectivity of these inhibitors, and together with MD simulation and computational analysis, reveal a dynamic pathway between the metal binding exosite and the active site, providing key details of a previously proposed allosteric mode of inhibition. Collectively, this work provides insight into both direct and indirect mechanisms of inhibition for KLK4 that have broad implications for the enzymology of the serine protease superfamily, and may potentially be exploited for the design of therapeutic inhibitors. | ||
| + | |||
| + | Direct and indirect mechanisms of KLK4 inhibition revealed by structure and dynamics.,Riley BT, Ilyichova O, Costa MG, Porebski BT, de Veer SJ, Swedberg JE, Kass I, Harris JM, Hoke DE, Buckle AM Sci Rep. 2016 Oct 21;6:35385. doi: 10.1038/srep35385. PMID:27767076<ref>PMID:27767076</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4k1e" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Revision as of 11:06, 2 November 2016
Atomic resolution crystal structures of Kallikrein-Related Peptidase 4 complexed with a modified SFTI inhibitor FCQR
| |||||||||||
