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| | ==Crystal structure of LUSH from Drosophila melanogaster: apo protein== | | ==Crystal structure of LUSH from Drosophila melanogaster: apo protein== |
| - | <StructureSection load='1t14' size='340' side='right' caption='[[1t14]], [[Resolution|resolution]] 1.86Å' scene=''> | + | <StructureSection load='1t14' size='340' side='right'caption='[[1t14]], [[Resolution|resolution]] 1.86Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1t14]] 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=1T14 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T14 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1t14]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T14 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T14 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></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.86Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1oof|1oof]], [[1oog|1oog]], [[1ooh|1ooh]], [[1ooi|1ooi]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lush ([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'>[https://proteopedia.org/fgij/fg.htm?mol=1t14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t14 OCA], [https://pdbe.org/1t14 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t14 RCSB], [https://www.ebi.ac.uk/pdbsum/1t14 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t14 ProSAT]</span></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=1t14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t14 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t14 RCSB], [http://www.ebi.ac.uk/pdbsum/1t14 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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> | + | [https://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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t1/1t14_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t1/1t14_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </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]. | + | </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/main_output.php?pdb_ID=1t14 ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 1t14" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Drosophila melanogaster]] | | [[Category: Drosophila melanogaster]] |
| - | [[Category: Jones, D N.M]] | + | [[Category: Large Structures]] |
| - | [[Category: Kruse, S W]] | + | [[Category: Jones DNM]] |
| - | [[Category: Alcohol]] | + | [[Category: Kruse SW]] |
| - | [[Category: Lush]]
| + | |
| - | [[Category: Odorant binding]]
| + | |
| - | [[Category: Transport protein]]
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| Structural highlights
Function
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.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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.
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[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kim MS, Repp A, Smith DP. LUSH odorant-binding protein mediates chemosensory responses to alcohols in Drosophila melanogaster. Genetics. 1998 Oct;150(2):711-21. PMID:9755202
- ↑ Kim MS, Smith DP. The invertebrate odorant-binding protein LUSH is required for normal olfactory behavior in Drosophila. Chem Senses. 2001 Feb;26(2):195-9. PMID:11238251
- ↑ Zhou JJ, Zhang GA, Huang W, Birkett MA, Field LM, Pickett JA, Pelosi P. Revisiting the odorant-binding protein LUSH of Drosophila melanogaster: evidence for odour recognition and discrimination. FEBS Lett. 2004 Jan 30;558(1-3):23-6. PMID:14759510 doi:10.1016/S0014-5793(03)01521-7
- ↑ Xu P, Atkinson R, Jones DN, Smith DP. Drosophila OBP LUSH is required for activity of pheromone-sensitive neurons. Neuron. 2005 Jan 20;45(2):193-200. PMID:15664171 doi:10.1016/j.neuron.2004.12.031
- ↑ Ha TS, Smith DP. A pheromone receptor mediates 11-cis-vaccenyl acetate-induced responses in Drosophila. J Neurosci. 2006 Aug 23;26(34):8727-33. PMID:16928861 doi:10.1523/JNEUROSCI.0876-06.2006
- ↑ Benton R, Vannice KS, Vosshall LB. An essential role for a CD36-related receptor in pheromone detection in Drosophila. Nature. 2007 Nov 8;450(7167):289-93. Epub 2007 Oct 17. PMID:17943085 doi:10.1038/nature06328
- ↑ Thode AB, Kruse SW, Nix JC, Jones DN. The role of multiple hydrogen-bonding groups in specific alcohol binding sites in proteins: insights from structural studies of LUSH. J Mol Biol. 2008 Mar 7;376(5):1360-76. Epub 2008 Jan 5. PMID:18234222 doi:http://dx.doi.org/10.1016/j.jmb.2007.12.063
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