4muv: Difference between revisions
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==M. loti cyclic-nucleotide binding domain mutant displaying inverted ligand selectivity, cyclic-GMP bound== | ==M. loti cyclic-nucleotide binding domain mutant displaying inverted ligand selectivity, cyclic-GMP bound== | ||
<StructureSection load='4muv' size='340' side='right' caption='[[4muv]], [[Resolution|resolution]] 1.25Å' scene=''> | <StructureSection load='4muv' size='340' side='right'caption='[[4muv]], [[Resolution|resolution]] 1.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4muv]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MUV OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4muv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mesorhizobium_japonicum_MAFF_303099 Mesorhizobium japonicum MAFF 303099]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MUV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MUV FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.25Å</td></tr> | ||
<tr><td class="sblockLbl"><b>[[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PCG:CYCLIC+GUANOSINE+MONOPHOSPHATE'>PCG</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4muv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4muv OCA], [https://pdbe.org/4muv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4muv RCSB], [https://www.ebi.ac.uk/pdbsum/4muv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4muv ProSAT]</span></td></tr> | ||
<table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/CNGK1_RHILO CNGK1_RHILO] Cyclic nucleotide-regulated potassium channel activated by cAMP.<ref>PMID:15550244</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cyclic nucleotide-binding (CNB) domains regulate the activity of channels, kinases, exchange factors, and transcription factors. These proteins are highly variable in their ligand selectivity; some are highly selective for either cAMP or cGMP, whereas others are not. Several molecular determinants of ligand selectivity in CNB domains have been defined, but these do not provide a complete view of the selectivity mechanism. We performed a thorough analysis of the ligand-binding properties of mutants of the CNB domain from the MlotiK1 potassium channel. In particular, we defined which residues specifically favor cGMP or cAMP. Inversion of ligand selectivity, from favoring cAMP to favoring cGMP, was only achieved through a combination of three mutations in the ligand-binding pocket. We determined the x-ray structure of the triple mutant bound to cGMP and performed molecular dynamics simulations and a biochemical analysis of the effect of the mutations. We concluded that the increase in cGMP affinity and selectivity does not result simply from direct interactions between the nucleotide base and the amino acids introduced in the ligand-binding pocket residues. Rather, tighter cGMP binding over cAMP results from the polar chemical character of the mutations, from greater accessibility of water molecules to the ligand in the bound state, and from an increase in the structural flexibility of the mutated binding pocket. | |||
Determinants of ligand selectivity in a cyclic nucleotide-regulated potassium channel.,Pessoa J, Fonseca F, Furini S, Morais-Cabral JH J Gen Physiol. 2014 Jul;144(1):41-54. PMID:24981229<ref>PMID:24981229</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4muv" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ion channels 3D structures|Ion channels 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mesorhizobium japonicum MAFF 303099]] | ||
[[Category: | [[Category: Fonseca F]] | ||
[[Category: | [[Category: Morais-Cabral JH]] | ||
[[Category: | [[Category: Pessoa J]] | ||