6ftf: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='6ftf' size='340' side='right'caption='[[6ftf]], [[Resolution|resolution]] 1.09Å' scene=''> | <StructureSection load='6ftf' size='340' side='right'caption='[[6ftf]], [[Resolution|resolution]] 1.09Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6ftf]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FTF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FTF FirstGlance]. <br> | <table><tr><td colspan='2'>[[6ftf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycc Trycc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FTF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FTF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7CI:7-cyano-7-deazainosine'>7CI</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7CI:7-cyano-7-deazainosine'>7CI</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tc00.1047053506227.150 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=353153 TRYCC])</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=6ftf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ftf OCA], [http://pdbe.org/6ftf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ftf RCSB], [http://www.ebi.ac.uk/pdbsum/6ftf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ftf ProSAT]</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=6ftf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ftf OCA], [http://pdbe.org/6ftf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ftf RCSB], [http://www.ebi.ac.uk/pdbsum/6ftf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ftf ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Protein kinase A (PKA), the main effector of cAMP in eukaryotes, is a paradigm for the mechanisms of ligand-dependent and allosteric regulation in signalling. Here we report the orthologous but cAMP-independent PKA of the protozoan Trypanosoma and identify 7-deaza-nucleosides as potent activators (EC50 >/= 6.5 nM) and high affinity ligands (KD >/= 8 nM). A co-crystal structure of trypanosome PKA with 7-cyano-7-deazainosine and molecular docking show how substitution of key amino acids in both CNB domains of the regulatory subunit and its unique C-terminal alphaD helix account for this ligand swap between trypanosome PKA and canonical cAMP-dependent PKAs. We propose nucleoside-related endogenous activators of Trypanosoma brucei PKA (TbPKA). The existence of eukaryotic CNB domains not associated with binding of cyclic nucleotides suggests that orphan CNB domains in other eukaryotes may bind undiscovered signalling molecules. Phosphoproteome analysis validates 7-cyano-7-deazainosine as powerful cell-permeable inducer to explore cAMP-independent PKA signalling in medically important neglected pathogens. | |||
Nucleoside analogue activators of cyclic AMP-independent protein kinase A of Trypanosoma.,Bachmaier S, Volpato Santos Y, Kramer S, Githure GB, Klockner T, Pepperl J, Baums C, Schenk R, Schwede F, Genieser HG, Dupuy JW, Forne I, Imhof A, Basquin J, Lorentzen E, Boshart M Nat Commun. 2019 Mar 29;10(1):1421. doi: 10.1038/s41467-019-09338-z. PMID:30926779<ref>PMID:30926779</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6ftf" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Trycc]] | |||
[[Category: Basquin, J]] | [[Category: Basquin, J]] | ||
[[Category: Boshart, M]] | [[Category: Boshart, M]] | ||
Latest revision as of 10:48, 10 April 2019
Regulatory subunit of a cAMP-independent protein kinase A from Trypanosoma cruzi at 1.09 A resolutionRegulatory subunit of a cAMP-independent protein kinase A from Trypanosoma cruzi at 1.09 A resolution
Structural highlights
Publication Abstract from PubMedProtein kinase A (PKA), the main effector of cAMP in eukaryotes, is a paradigm for the mechanisms of ligand-dependent and allosteric regulation in signalling. Here we report the orthologous but cAMP-independent PKA of the protozoan Trypanosoma and identify 7-deaza-nucleosides as potent activators (EC50 >/= 6.5 nM) and high affinity ligands (KD >/= 8 nM). A co-crystal structure of trypanosome PKA with 7-cyano-7-deazainosine and molecular docking show how substitution of key amino acids in both CNB domains of the regulatory subunit and its unique C-terminal alphaD helix account for this ligand swap between trypanosome PKA and canonical cAMP-dependent PKAs. We propose nucleoside-related endogenous activators of Trypanosoma brucei PKA (TbPKA). The existence of eukaryotic CNB domains not associated with binding of cyclic nucleotides suggests that orphan CNB domains in other eukaryotes may bind undiscovered signalling molecules. Phosphoproteome analysis validates 7-cyano-7-deazainosine as powerful cell-permeable inducer to explore cAMP-independent PKA signalling in medically important neglected pathogens. Nucleoside analogue activators of cyclic AMP-independent protein kinase A of Trypanosoma.,Bachmaier S, Volpato Santos Y, Kramer S, Githure GB, Klockner T, Pepperl J, Baums C, Schenk R, Schwede F, Genieser HG, Dupuy JW, Forne I, Imhof A, Basquin J, Lorentzen E, Boshart M Nat Commun. 2019 Mar 29;10(1):1421. doi: 10.1038/s41467-019-09338-z. PMID:30926779[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||