6fdk
From Proteopedia
(Difference between revisions)
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6fdk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chlamydia_trachomatis_434/Bu Chlamydia trachomatis 434/Bu] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FDK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FDK FirstGlance]. <br> | <table><tr><td colspan='2'>[[6fdk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chlamydia_trachomatis_434/Bu Chlamydia trachomatis 434/Bu] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FDK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FDK FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AYE:PROP-2-EN-1-AMINE'>AYE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AYE:PROP-2-EN-1-AMINE'>AYE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=6fdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fdk OCA], [https://pdbe.org/6fdk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fdk RCSB], [https://www.ebi.ac.uk/pdbsum/6fdk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fdk ProSAT]</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=6fdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fdk OCA], [https://pdbe.org/6fdk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fdk RCSB], [https://www.ebi.ac.uk/pdbsum/6fdk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fdk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/CDUB1_CHLT2 CDUB1_CHLT2] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protease possesses deubiquitinating and deneddylating activities (By similarity). Impairs ubiquitination and degradation of NF-kappa-B inhibitor alpha (NFKBIA), thereby preventing NF-kappa-B activation.<ref>PMID:18503636</ref> | [https://www.uniprot.org/uniprot/CDUB1_CHLT2 CDUB1_CHLT2] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protease possesses deubiquitinating and deneddylating activities (By similarity). Impairs ubiquitination and degradation of NF-kappa-B inhibitor alpha (NFKBIA), thereby preventing NF-kappa-B activation.<ref>PMID:18503636</ref> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Based on the similarity between the active sites of the deubiquitylating and deneddylating enzyme ChlaDub1 (Cdu1) and the evolutionary related protease adenain a target-hopping approach screening on a focused set of adenain inhibitors has been pursued. The thereby identified cyano-pyrimidine based inhibitors represent the first active-site directed small molecule inhibitors for Cdu1. High-resolution crystal structures of Cdu1 in complex with two covalently bound cyano-pyrimidines as well as with its substrate ubiquitin have been obtained. These structural data were complemented by enzymatic assays and covalent docking studies to provide insight into Cdu1s substrate recognition, active site pocket flexibility and potential hotspots for ligand interaction. Combined, these data provide a strong foundation for future structure-guided medicinal chemistry optimization of this cyano-pyrimidine based scaffold towards more potent and specific Cdu1 inhibitors. | ||
| - | |||
| - | Structural basis of substrate recognition and covalent inhibition of Cdu1 from Chlamydia trachomatis.,Ramirez YA, Adler T, Altmann E, Tiesmeyer C, Klemm T, Sauer F, Kathman S, Statsyuk A, Sotriffer C, Kisker C ChemMedChem. 2018 Jul 20. doi: 10.1002/cmdc.201800364. PMID:30028574<ref>PMID:30028574</ref> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 6fdk" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Structure of Chlamydia trachomatis effector protein Cdu1 bound to ubiquitin
| |||||||||||
