6fdq

From Proteopedia

(Difference between revisions)

Current revision

Structure of Chlamydia trachomatis effector protein Cdu1 bound to Compound 5

Structural highlights

6fdq is a 2 chain structure with sequence from Chlt2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	6fdk
Gene:	cdu1, CTL0247 (CHLT2)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Le Negrate G, Krieg A, Faustin B, Loeffler M, Godzik A, Krajewski S, Reed JC. ChlaDub1 of Chlamydia trachomatis suppresses NF-kappaB activation and inhibits IkappaBalpha ubiquitination and degradation. Cell Microbiol. 2008 Sep;10(9):1879-92. doi: 10.1111/j.1462-5822.2008.01178.x., Epub 2008 Jun 28. PMID:18503636 doi:http://dx.doi.org/10.1111/j.1462-5822.2008.01178.x
↑ Ramirez YA, Adler T, Altmann E, Tiesmeyer C, Klemm T, Sauer F, Kathman S, Statsyuk A, Sotriffer C, Kisker C. Structural basis of substrate recognition and covalent inhibition of Cdu1 from Chlamydia trachomatis. ChemMedChem. 2018 Jul 20. doi: 10.1002/cmdc.201800364. PMID:30028574 doi:http://dx.doi.org/10.1002/cmdc.201800364

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6fdq"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6fdq is ON HOLD
+==Structure of Chlamydia trachomatis effector protein Cdu1 bound to Compound 5==
+<StructureSection load='6fdq' size='340' side='right' caption='[[6fdq]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6fdq]] 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=6FDQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FDQ FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2UQ:N-BENZYL-2-[(Z)-IMINOMETHYL]PYRIMIDINE-5-CARBOXAMIDE'>2UQ</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6fdk|6fdk]]</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=6fdq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fdq OCA], [http://pdbe.org/6fdq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fdq RCSB], [http://www.ebi.ac.uk/pdbsum/6fdq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fdq 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>
+<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.
-Authors: Ramirez, Y., Kisker, C., Altmann, E.
+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>
-Description: Structure of Chlamydia trachomatis effector protein Cdu1 bound to Compound 5
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Ramirez, Y]]
+<div class="pdbe-citations 6fdq" style="background-color:#fffaf0;"></div>
-[[Category: Kisker, C]]
+== 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]]

6fdq

From Proteopedia

Current revision

Structure of Chlamydia trachomatis effector protein Cdu1 bound to Compound 5

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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