View source for 8vsx


==NMR Structure of GCAP5 R22A==
<StructureSection load='8vsx' size='340' side='right'caption='[[8vsx]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vsx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8VSX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VSX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</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=8vsx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vsx OCA], [https://pdbe.org/8vsx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vsx RCSB], [https://www.ebi.ac.uk/pdbsum/8vsx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vsx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q5MAC8_DANRE Q5MAC8_DANRE] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Guanylate cyclase activating protein-5 (GCAP5) in zebrafish photoreceptors promotes the activation of membrane receptor retinal guanylate cyclase (GC-E). Previously, we showed the R22A mutation in GCAP5 (GCAP5(R22A)) abolishes dimerization of GCAP5 and activates GC-E by more than 3-fold compared to that of wild-type GCAP5 (GCAP5(WT)). Here, we present ITC, NMR, and functional analysis of GCAP5(R22A) to understand how R22A causes a decreased dimerization affinity and increased cyclase activation. ITC experiments reveal GCAP5(R22A) binds a total of 3 Ca(2+), including two sites in the nanomolar range followed by a single micromolar site. The two nanomolar sites in GCAP5(WT) were not detected by ITC, suggesting that R22A may affect the binding of Ca(2+) to these sites. The NMR-derived structure of GCAP5(R22A) is overall similar to that of GCAP5(WT) (RMSD = 2.3 A), except for local differences near R22A (Q19, W20, Y21, and K23) and an altered orientation of the C-terminal helix near the N-terminal myristate. GCAP5(R22A) lacks an intermolecular salt bridge between R22 and D71 that may explain the weakened dimerization. We present a structural model of GCAP5 bound to GC-E in which the R22 side-chain contacts exposed hydrophobic residues in GC-E. Cyclase assays suggest that GC-E binds to GCAP5(R22A) with approximately 25% higher affinity compared to GCAP5(WT), consistent with more favorable hydrophobic contact by R22A that may help explain the increased cyclase activation.

NMR Structure of Retinal Guanylate Cyclase Activating Protein 5 (GCAP5) with R22A Mutation That Abolishes Dimerization and Enhances Cyclase Activation.,Cudia DL, Ahoulou EO, Bej A, Janssen AN, Scholten A, Koch KW, Ames JB Biochemistry. 2024 Apr 25. doi: 10.1021/acs.biochem.4c00046. PMID:38662574<ref>PMID:38662574</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8vsx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Danio rerio]]
[[Category: Large Structures]]
[[Category: Ames JB]]
[[Category: Cudia DL]]