PDBsum entry 1as2

Signal transduction

PDB id

1as2

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Contents

			Protein chain

					315 a.a. *

			Ligands

					PO4


					GDP

			Waters ×5

* Residue conservation analysis

PDB id:

1as2

Links
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Name:

Signal transduction

Title:

Gdp+pi bound g42v gia1

Structure:

Gia1. Chain: a. Engineered: yes. Mutation: yes. Other_details: gdp+pi bound g42v gia1

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Cell_line: bl21. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.80Å

R-factor:

0.189

R-free:

0.250

Authors:

A.S.Raw,D.E.Coleman,A.G.Gilman,S.R.Sprang

Key ref:

A.S.Raw et al. (1997). Structural and biochemical characterization of the GTPgammaS-, GDP.Pi-, and GDP-bound forms of a GTPase-deficient Gly42 --> Val mutant of Gialpha1. Biochemistry, 36, 15660-15669. PubMed id: 9398294 DOI: 10.1021/bi971912p

Date:

11-Aug-97

Release date:

12-Nov-97

PROCHECK

	Headers

	References

Protein chain

P10824 (GNAI1_RAT) - Guanine nucleotide-binding protein G(i) subunit alpha-1 from Rattus norvegicus

Seq: Struc:					354 a.a. 315 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 1 residue position (black cross)



		Enzyme reactions

Enzyme class:

E.C.?

[IntEnz] [ExPASy] [KEGG] [BRENDA]

DOI no: 10.1021/bi971912p	Biochemistry 36:15660-15669 (1997)
PubMed id: 9398294

Structural and biochemical characterization of the GTPgammaS-, GDP.Pi-, and GDP-bound forms of a GTPase-deficient Gly42 --> Val mutant of Gialpha1.
A.S.Raw, D.E.Coleman, A.G.Gilman, S.R.Sprang.

ABSTRACT

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.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20457940

A.Zurita, Y.Zhang, L.Pedersen, T.Darden, and L.Birnbaumer (2010).
Obligatory role in GTP hydrolysis for the amide carbonyl oxygen of the Mg(2+)-coordinating Thr of regulatory GTPases.

Proc Natl Acad Sci U S A, 107, 9596-9601.

20731539

L.Birnbaumer, and A.R.Zurita (2010).
On the roles of Mg in the activation of G proteins.

J Recept Signal Transduct Res, 30, 372-375.

18175322

L.Qu, J.Wan, Y.Cao, Y.Zhang, R.Chen, and Y.Huang (2008).
Analyzing and modeling the inhibitory effect of phosphatidic acid on the GTP-gamma-S binding activity of Goalpha.

Proteins, 71, 1732-1743.

17264214

C.A.Johnston, and D.P.Siderovski (2007).
Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity.

Proc Natl Acad Sci U S A, 104, 2001-2006.

PDB code:

2hlb

16469737

S.Majumdar, S.Ramachandran, and R.A.Cerione (2006).
New insights into the role of conserved, essential residues in the GTP binding/GTP hydrolytic cycle of large G proteins.

J Biol Chem, 281, 9219-9226.

15837192

S.Pasqualato, and J.Cherfils (2005).
Crystallographic evidence for substrate-assisted GTP hydrolysis by a small GTP binding protein.

Structure, 13, 533-540.

PDB code:

1oix

15546818

X.Gao, Z.Du, and T.B.Patel (2005).
Copper and zinc inhibit Galphas function: a nucleotide-free state of Galphas induced by Cu2+ and Zn2+.

J Biol Chem, 280, 2579-2586.

15128951

C.J.Thomas, X.Du, P.Li, Y.Wang, E.M.Ross, and S.R.Sprang (2004).
Uncoupling conformational change from GTP hydrolysis in a heterotrimeric G protein alpha-subunit.

Proc Natl Acad Sci U S A, 101, 7560-7565.

PDB codes:

1svk 1svs

15189875

J.D.Lawson, E.Pate, I.Rayment, and R.G.Yount (2004).
Molecular dynamics analysis of structural factors influencing back door pi release in myosin.

Biophys J, 86, 3794-3803.

14704167

C.A.Bastiani, S.Gharib, M.I.Simon, and P.W.Sternberg (2003).
Caenorhabditis elegans Galphaq regulates egg-laying behavior via a PLCbeta-independent and serotonin-dependent signaling pathway and likely functions both in the nervous system and in muscle.

Genetics, 165, 1805-1822.

14622106

M.Natochin, and N.O.Artemyev (2003).
A point mutation uncouples transducin-alpha from the photoreceptor RGS and effector proteins.

J Neurochem, 87, 1262-1271.

12021440

F.Fabiola, R.Bertram, A.Korostelev, and M.S.Chapman (2002).
An improved hydrogen bond potential: impact on medium resolution protein structures.

Protein Sci, 11, 1415-1423.

10657303

C.Fenwick, S.Y.Na, R.E.Voll, H.Zhong, S.Y.Im, J.W.Lee, and S.Ghosh (2000).
A subclass of Ras proteins that regulate the degradation of IkappaB.

Science, 287, 869-873.

10966476

E.M.Ross, and T.M.Wilkie (2000).
GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins.

Annu Rev Biochem, 69, 795-827.

10702259

K.G.Muradov, and N.O.Artemyev (2000).
Loss of the effector function in a transducin-alpha mutant associated with Nougaret night blindness.

J Biol Chem, 275, 6969-6974.

10705368

L.Kallal, and R.Fishel (2000).
The GTP hydrolysis defect of the Saccharomyces cerevisiae mutant G-protein Gpa1(G50V).

Yeast, 16, 387-400.

10358003

D.E.Coleman, and S.R.Sprang (1999).
Structure of Gialpha1.GppNHp, autoinhibition in a galpha protein-substrate complex.

J Biol Chem, 274, 16669-16672.

PDB code:

1cip

10494851

J.Müller, A.Marx, S.Sack, Y.H.Song, and E.Mandelkow (1999).
The structure of the nucleotide-binding site of kinesin.

Biol Chem, 380, 981-992.

9772163

D.E.Coleman, and S.R.Sprang (1998).
Crystal structures of the G protein Gi alpha 1 complexed with GDP and Mg2+: a crystallographic titration experiment.

Biochemistry, 37, 14376-14385.

PDB code:

1bof

9792679

E.H.Bursey, and B.K.Burgess (1998).
The role of methionine 156 in cross-subunit nucleotide interactions in the iron protein of nitrogenase.

J Biol Chem, 273, 29678-29685.

9631293

S.J.Gamblin, and S.J.Smerdon (1998).
GTPase-activating proteins and their complexes.

Curr Opin Struct Biol, 8, 195-201.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.