View source for 6fdu


==Structure of Chlamydia trachomatis effector protein Cdu1 bound to Compound 3==
<StructureSection load='6fdu' size='340' side='right' caption='[[6fdu]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fdu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Chlt2 Chlt2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FDU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FDU FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=D5W:(2~{S},3~{S})-2-[[(2~{S})-2-[3,5-bis(chloranyl)phenyl]-2-(dimethylamino)ethanoyl]amino]-~{N}-[[2-(iminomethyl)pyrimidin-4-yl]methyl]-3-methyl-pentanamide'>D5W</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6fdk|6fdk]], [[6fdq|6fdq]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cdu1, CTL0247 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=471472 CHLT2])</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=6fdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fdu OCA], [http://pdbe.org/6fdu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fdu RCSB], [http://www.ebi.ac.uk/pdbsum/6fdu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fdu ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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>  
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fdu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Chlt2]]
[[Category: Altmann, E]]
[[Category: Kisker, C]]
[[Category: Ramirez, Y]]
[[Category: Ce protease]]
[[Category: Chladub1]]
[[Category: Covalent inhibitor]]
[[Category: Dub]]
[[Category: Hydrolase]]
[[Category: Ubiquitin]]