View source for 2mzk


==The solution structure of the Magnesium-bound Conantokin RLB==
<StructureSection load='2mzk' size='340' side='right'caption='[[2mzk]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2mzk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_rolani Conus rolani]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MZK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 10 models</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CGU:GAMMA-CARBOXY-GLUTAMIC+ACID'>CGU</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=2mzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mzk OCA], [https://pdbe.org/2mzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mzk RCSB], [https://www.ebi.ac.uk/pdbsum/2mzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mzk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CKR1B_CONRO CKR1B_CONRO] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Conantokins are ~20 amino acid peptides present in predatory marine snail venoms that function as allosteric antagonists of ion channels of the N-methyl-D-aspartate receptor (NMDAR). These peptides possess a high percentage of post-/co-translationally modified amino acids, particularly gamma-carboxyglutamate (Gla). Appropriately spaced Gla residues allow binding of functional divalent cations, which induces end-to-end alpha-helices in many conantokins. A smaller number of these peptides additionally contain 4-hydroxyproline (HyP). HyP should prevent adoption of the metal ion-induced full alpha-helix, with unknown functional consequences. To address this disparity, as well as the role of HyP in conantokins, we have solved the high-resolution 3D-solution structure of a Gla/HyP-containing 18-residue conantokin, conRl-B, by high-field NMR spectroscopy. We show that HyP10 disrupts only a small region of the alpha-helix of the Mg2+/peptide complex, which displays cation-induced alpha-helices on each terminus of the peptide. The function of conRl-B was examined by measuring its inhibition of NMDA/Gly-mediated current through NMDAR ion channels in mouse cortical neurons. ConRl-B displays high inhibitory selectivity for subclasses of NMDARs that contain the functionally important GluN2B subunit. Replacement of HyP10 with N8Q results in a Mg2+-complexed end-to-end alpha-helix, accompanied by attenuation of NMDAR inhibitory activity. However, replacement of HyP10 with Pro10 allowed the resulting peptide to retain its inhibitory property, but diminished its GluN2B-specificity. Thus, these modified amino acids, in specific peptide backbones, play critical roles in their subunit-selective inhibition of NMDAR ion channels, a finding that can be employed to design NMDAR antagonists that function at ion channels of distinct NMDAR subclasses.

Hydroxyproline-induced Helical Disruption in Conantokin Rl-B Affects Subunit-selective Antagonistic Activities Toward Ion Channels of NMDA Receptors.,Kunda S, Yuan Y, Balsara RD, Zaijcek J, Castellino FJ J Biol Chem. 2015 Jun 5. pii: jbc.M115.650341. PMID:26048991<ref>PMID:26048991</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2mzk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Conus rolani]]
[[Category: Large Structures]]
[[Category: Balsara RD]]
[[Category: Castellino FJ]]
[[Category: Kunda S]]
[[Category: Yuan Y]]
[[Category: Zajicek J]]