3b86: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-{{STRUCTURE_3b86|  PDB=3b86  |  SCENE=  }}
+==Crystal structure of T57S substituted LUSH protein complexed with ethanol==
-===Crystal structure of T57S substituted LUSH protein complexed with ethanol===
+<StructureSection load='3b86' size='340' side='right' caption='[[3b86]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
-{{ABSTRACT_PUBMED_18234222}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3b86]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B86 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3B86 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ooh|1ooh]], [[1oof|1oof]], [[1oog|1oog]], [[1ooi|1ooi]], [[1t14|1t14]], [[3b6x|3b6x]], [[3b7a|3b7a]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lush, Obp76a, Obp76c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster])</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=3b86 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b86 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3b86 RCSB], [http://www.ebi.ac.uk/pdbsum/3b86 PDBsum]</span></td></tr>
+</table>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b8/3b86_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+It is now generally accepted that many of the physiological effects of alcohol consumption are a direct result of binding to specific sites in neuronal proteins such as ion channels or other components of neuronal signaling cascades. Binding to these targets generally occurs in water-filled pockets and leads to alterations in protein structure and dynamics. However, the precise interactions required to confer alcohol sensitivity to a particular protein remain undefined. Using information from the previously solved crystal structures of the Drosophila melanogaster protein LUSH in complexes with short-chain alcohols, we have designed and tested the effects of specific amino acid substitutions on alcohol binding. The effects of these substitutions, specifically S52A, T57S, and T57A, were examined using a combination of molecular dynamics, X-ray crystallography, fluorescence spectroscopy, and thermal unfolding. These studies reveal that the binding of ethanol is highly sensitive to small changes in the composition of the alcohol binding site. We find that T57 is the most critical residue for binding alcohols; the T57A substitution completely abolishes binding, while the T57S substitution differentially affects ethanol binding compared to longer-chain alcohols. The additional requirement for a potential hydrogen-bond acceptor at position 52 suggests that both the presence of multiple hydrogen-bonding groups and the identity of the hydrogen-bonding residues are critical for defining an ethanol binding site. These results provide new insights into the detailed chemistry of alcohol's interactions with proteins.
-==Function==
+The role of multiple hydrogen-bonding groups in specific alcohol binding sites in proteins: insights from structural studies of LUSH.,Thode AB, Kruse SW, Nix JC, Jones DN J Mol Biol. 2008 Mar 7;376(5):1360-76. Epub 2008 Jan 5. PMID:18234222<ref>PMID:18234222</ref>
-[[http://www.uniprot.org/uniprot/OB76A_DROME OB76A_DROME]] Odorant-binding protein required for olfactory behavior and for activity of pheromone-sensitive neurons. Binds to alcohols and mediates avoidance behavior to high concentrations of alcohols, the alcohol-binding possibly resulting in activation of receptors on T2B neurons, the activation of these receptors inhibiting these neurons. Acts in concert with Snmp and lush to capture cVA molecules on the surface of Or67d expressing olfactory dendrites and facilitate their transfer to the odorant-receptor Orco complex. Required for cVA response, probably by binding to VA. May act by serving as an adapter that bridges the presence of gaseous pheromone molecules, cVA, to activation of specific neuronal receptors expressed on T1 olfactory neurons, possibly via a specific conformational change induced by cVA that in turn activates T1 receptors. T1 neurons are excited by the pheromone VA, while T2 neurons are inhibited by alcohols. Also binds to phthalates.<ref>PMID:9755202</ref> <ref>PMID:11238251</ref> <ref>PMID:14759510</ref> <ref>PMID:15664171</ref> <ref>PMID:16928861</ref> <ref>PMID:17943085</ref>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[3b86]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B86 OCA].
+</div>
-==Reference==
+==See Also==
-<ref group="xtra">PMID:018234222</ref><references group="xtra"/><references/>
+*[[Odorant binding protein|Odorant binding protein]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Drosophila melanogaster]]
 [[Category: Jones, D N.M]]