1as3
From Proteopedia
(New page: 200px<br /><applet load="1as3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1as3, resolution 2.4Å" /> '''GDP BOUND G42V GIA1''...) |
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| - | [[Image:1as3.jpg|left|200px]]<br /><applet load="1as3" size=" | + | [[Image:1as3.jpg|left|200px]]<br /><applet load="1as3" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1as3, resolution 2.4Å" /> | caption="1as3, resolution 2.4Å" /> | ||
'''GDP BOUND G42V GIA1'''<br /> | '''GDP BOUND G42V GIA1'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The Gly42 --> Val mutant of Gialpha1 was characterized structurally and | + | The Gly42 --> Val mutant of Gialpha1 was characterized structurally and biochemically to elucidate two important features of Gialpha1-catalyzed GTP hydrolysis. The crystal structure of the GTPgammaS-bound G42VGialpha1 protein demonstrates that the steric bulk of Val42 pushes the Gln204 residue into a catalytically incompetent conformation, providing a rationale for the diminished GTPase activity of this mutant. The same phenomenon may also account for the diminished GTPase activity of the homologous transforming Gly42 --> Val mutation in p21(ras). Similarly, the steric bulk of the unique Ser42 residue in Gzalpha may account for the comparatively slower rate of GTP hydrolysis by this Galpha subunit. The G42VGialpha1 subunit was also characterized structurally in its GDP.Pi- and GDP-bound states, providing a unique opportunity to view three "snapshots" of GTP hydrolysis. Hydrolysis of GTP to a transient GDP.Pi-bound intermediate is associated with substantial conformational changes in the switch II segment of the protein. Eventual release of Pi results in further removal of switch I from the active site and a highly mobile switch II segment. Despite their disparate biochemical properties, the structural similarity of G42VGialpha1 to the G203AGialpha1 mutant in the GDP.Pi-bound form suggests that both mutations stabilize a conformation of the GDP. Pi-bound protein that occurs only transiently in the wild-type protein. The structures of the GDP-bound forms of the wild-type and mutant proteins are similar. |
==About this Structure== | ==About this Structure== | ||
| - | 1AS3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with SO4 and GDP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1AS3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AS3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Coleman, D | + | [[Category: Coleman, D E.]] |
| - | [[Category: Gilman, A | + | [[Category: Gilman, A G.]] |
| - | [[Category: Raw, A | + | [[Category: Raw, A S.]] |
| - | [[Category: Sprang, S | + | [[Category: Sprang, S R.]] |
[[Category: GDP]] | [[Category: GDP]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
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[[Category: signal transduction]] | [[Category: signal transduction]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:47:44 2008'' |
Revision as of 09:47, 21 February 2008
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GDP BOUND G42V GIA1
Overview
The Gly42 --> Val mutant of Gialpha1 was characterized structurally and biochemically to elucidate two important features of Gialpha1-catalyzed GTP hydrolysis. The crystal structure of the GTPgammaS-bound G42VGialpha1 protein demonstrates that the steric bulk of Val42 pushes the Gln204 residue into a catalytically incompetent conformation, providing a rationale for the diminished GTPase activity of this mutant. The same phenomenon may also account for the diminished GTPase activity of the homologous transforming Gly42 --> Val mutation in p21(ras). Similarly, the steric bulk of the unique Ser42 residue in Gzalpha may account for the comparatively slower rate of GTP hydrolysis by this Galpha subunit. The G42VGialpha1 subunit was also characterized structurally in its GDP.Pi- and GDP-bound states, providing a unique opportunity to view three "snapshots" of GTP hydrolysis. Hydrolysis of GTP to a transient GDP.Pi-bound intermediate is associated with substantial conformational changes in the switch II segment of the protein. Eventual release of Pi results in further removal of switch I from the active site and a highly mobile switch II segment. Despite their disparate biochemical properties, the structural similarity of G42VGialpha1 to the G203AGialpha1 mutant in the GDP.Pi-bound form suggests that both mutations stabilize a conformation of the GDP. Pi-bound protein that occurs only transiently in the wild-type protein. The structures of the GDP-bound forms of the wild-type and mutant proteins are similar.
About this Structure
1AS3 is a Single protein structure of sequence from Rattus norvegicus with and as ligands. Full crystallographic information is available from OCA.
Reference
Structural and biochemical characterization of the GTPgammaS-, GDP.Pi-, and GDP-bound forms of a GTPase-deficient Gly42 --> Val mutant of Gialpha1., Raw AS, Coleman DE, Gilman AG, Sprang SR, Biochemistry. 1997 Dec 16;36(50):15660-9. PMID:9398294
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