3ah8

From Proteopedia

(Difference between revisions)

Revision as of 14:52, 29 December 2021

Structure of heterotrimeric G protein Galpha-q beta gamma in complex with an inhibitor YM-254890

Structural highlights

3ah8 is a 4 chain structure with sequence from Bovin, Chromobacterium sp. and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:	, , , , , ,
Gene:	gmhB (LK3 transgenic mice), GNB1 (BOVIN), GNG2 (BOVIN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GNAI1_RAT] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.^[1] [GBG2_BOVIN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. [GBB1_BOVIN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.

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

Heterotrimeric GTP-binding proteins (G proteins) transmit extracellular stimuli perceived by G protein-coupled receptors (GPCRs) to intracellular signaling cascades. Hundreds of GPCRs exist in humans and are the targets of a large percentage of the pharmaceutical drugs used today. Because G proteins are regulated by GPCRs, small molecules that directly modulate G proteins have the potential to become therapeutic agents. However, strategies to develop modulators have been hampered by a lack of structural knowledge of targeting sites for specific modulator binding. Here we present the mechanism of action of the cyclic depsipeptide YM-254890, which is a recently discovered G(q)-selective inhibitor. YM-254890 specifically inhibits the GDP/GTP exchange reaction of alpha subunit of G(q) protein (Galpha(q)) by inhibiting the GDP release from Galpha(q). X-ray crystal structure analysis of the Galpha(q)betagamma-YM-254890 complex shows that YM-254890 binds the hydrophobic cleft between two interdomain linkers connecting the GTPase and helical domains of the Galpha(q). The binding stabilizes an inactive GDP-bound form through direct interactions with switch I and impairs the linker flexibility. Our studies provide a novel targeting site for the development of small molecules that selectively inhibit each Galpha subunit and an insight into the molecular mechanism of G protein activation.

Structural basis for the specific inhibition of heterotrimeric Gq protein by a small molecule.,Nishimura A, Kitano K, Takasaki J, Taniguchi M, Mizuno N, Tago K, Hakoshima T, Itoh H Proc Natl Acad Sci U S A. 2010 Jul 16. PMID:20639466^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Shu FJ, Ramineni S, Amyot W, Hepler JR. Selective interactions between Gi alpha1 and Gi alpha3 and the GoLoco/GPR domain of RGS14 influence its dynamic subcellular localization. Cell Signal. 2007 Jan;19(1):163-76. Epub 2006 Jul 25. PMID:16870394 doi:http://dx.doi.org/10.1016/j.cellsig.2006.06.002
↑ Nishimura A, Kitano K, Takasaki J, Taniguchi M, Mizuno N, Tago K, Hakoshima T, Itoh H. Structural basis for the specific inhibition of heterotrimeric Gq protein by a small molecule. Proc Natl Acad Sci U S A. 2010 Jul 16. PMID:20639466

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3ah8"

@@ Line 1: / Line 1: @@
 ==Structure of heterotrimeric G protein Galpha-q beta gamma in complex with an inhibitor YM-254890==
-<StructureSection load='3ah8' size='340' side='right' caption='[[3ah8]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+<StructureSection load='3ah8' size='340' side='right'caption='[[3ah8]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3ah8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin], [http://en.wikipedia.org/wiki/Chromobacterium_sp. Chromobacterium sp.] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AH8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3AH8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3ah8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin], [https://en.wikipedia.org/wiki/Chromobacterium_sp. Chromobacterium sp.] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AH8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AH8 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=DAM:N-METHYL-ALPHA-BETA-DEHYDROALANINE'>DAM</scene>, <scene name='pdbligand=HF2:(2R)-2-HYDROXY-3-PHENYLPROPANOIC+ACID'>HF2</scene>, <scene name='pdbligand=HL2:(2S,3R)-2-AMINO-3-HYDROXY-4-METHYLPENTANOIC+ACID'>HL2</scene>, <scene name='pdbligand=MAA:N-METHYL-L-ALANINE'>MAA</scene>, <scene name='pdbligand=OTH:N,O-DIMETHYL-L-THREONINE'>OTH</scene>, <scene name='pdbligand=THC:N-METHYLCARBONYLTHREONINE'>THC</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gmhB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), GNB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN]), GNG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gmhB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), GNB1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN]), GNG2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</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=3ah8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ah8 OCA], [http://pdbe.org/3ah8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ah8 RCSB], [http://www.ebi.ac.uk/pdbsum/3ah8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ah8 ProSAT]</span></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=3ah8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ah8 OCA], [https://pdbe.org/3ah8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ah8 RCSB], [https://www.ebi.ac.uk/pdbsum/3ah8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ah8 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GNAI1_RAT GNAI1_RAT]] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:16870394</ref>  [[http://www.uniprot.org/uniprot/GBG2_BOVIN GBG2_BOVIN]] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. [[http://www.uniprot.org/uniprot/GBB1_BOVIN GBB1_BOVIN]] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.
+[[https://www.uniprot.org/uniprot/GNAI1_RAT GNAI1_RAT]] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:16870394</ref>  [[https://www.uniprot.org/uniprot/GBG2_BOVIN GBG2_BOVIN]] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. [[https://www.uniprot.org/uniprot/GBB1_BOVIN GBB1_BOVIN]] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.
 == 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/ah/3ah8_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ah/3ah8_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 32: / Line 32: @@
 ==See Also==
-*[[Transducin|Transducin]]
+*[[Transducin 3D structures|Transducin 3D structures]]
 == References ==
 <references/>
@@ Line 39: / Line 39: @@
 [[Category: Bovin]]
 [[Category: Chromobacterium sp]]
+[[Category: Large Structures]]
 [[Category: Lk3 transgenic mice]]
 [[Category: Hakoshima, T]]

3ah8

From Proteopedia

Revision as of 14:52, 29 December 2021

Structure of heterotrimeric G protein Galpha-q beta gamma in complex with an inhibitor YM-254890

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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