View source for 5lxb


==Crystal structure of a mutant binding protein (5HTBP-AChBP) in complex with palonosetron==
<StructureSection load='5lxb' size='340' side='right'caption='[[5lxb]], [[Resolution|resolution]] 2.34&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5lxb]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LXB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LXB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.34&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7A9:PALONOSETRON'>7A9</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=5lxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lxb OCA], [https://pdbe.org/5lxb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lxb RCSB], [https://www.ebi.ac.uk/pdbsum/5lxb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lxb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8WSF8_APLCA Q8WSF8_APLCA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Palonosetron is a potent 5-HT3 receptor antagonist and an effective therapeutic agent against emesis. Here we identify the molecular determinants of compound recognition in the receptor binding site by obtaining a high resolution structure of palonosetron bound to an engineered acetylcholine binding protein that mimics the 5-HT3 receptor binding site, termed 5-HTBP, and by examining the potency of palonosetron in a range of 5-HT3 receptors with mutated binding site residues. The structural data indicate that palonosetron forms a tight and effective wedge in the binding pocket, made possible by its rigid tricyclic ring structure and its interactions with binding site residues; it adopts a binding pose that is distinct from the related antiemetics granisetron and tropisetron. The functional data show many residues previously shown to interact with agonists and antagonists in the binding site are important for palonosetron binding, and indicate those of particular importance are W183 (a cation-pi interaction and a hydrogen bond) and Y153 (a hydrogen bond). This information, and the availability of the structure of palonosetron bound to 5-HTBP, should aid the development of novel and more efficacious drugs that act via 5-HT3 receptors.

Palonosetron-5-HT3 Receptor Interactions As Shown by a Binding Protein Cocrystal Structure.,Price KL, Lillestol RK, Ulens C, Lummis SC ACS Chem Neurosci. 2016 Sep 22. PMID:27656911<ref>PMID:27656911</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5lxb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Aplysia californica]]
[[Category: Large Structures]]
[[Category: Ulens C]]