PDBsum entry 1cip

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Hydrolase PDB id
Protein chain
316 a.a. *
Waters ×157
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Gi-alpha-1 subunit of guanine nucleotide-binding protein complexed with a gtp analogue
Structure: Protein (guanine nucleotide-binding protein alpha-1 subunit). Chain: a. Synonym: gia1, guanine nucleotide-binding protein g(i), alpha-1 subunit. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.50Å     R-factor:   0.213     R-free:   0.235
Authors: D.Coleman,S.Sprang
Key ref:
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. PubMed id: 10358003 DOI: 10.1074/jbc.274.24.16669
05-Apr-99     Release date:   09-Apr-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P10824  (GNAI1_RAT) -  Guanine nucleotide-binding protein G(i) subunit alpha-1
354 a.a.
316 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     protein complex   11 terms 
  Biological process     cell cycle   7 terms 
  Biochemical function     nucleotide binding     11 terms  


DOI no: 10.1074/jbc.274.24.16669 J Biol Chem 274:16669-16672 (1999)
PubMed id: 10358003  
Structure of Gialpha1.GppNHp, autoinhibition in a galpha protein-substrate complex.
D.E.Coleman, S.R.Sprang.
The structure of the G protein Gialpha1 complexed with the nonhydrolyzable GTP analog guanosine-5'-(betagamma-imino)triphosphate (GppNHp) has been determined at a resolution of 1.5 A. In the active site of Gialpha1. GppNHp, a water molecule is hydrogen bonded to the side chain of Glu43 and to an oxygen atom of the gamma-phosphate group. The side chain of the essential catalytic residue Gln204 assumes a conformation which is distinctly different from that observed in complexes with either guanosine 5'-O-3-thiotriphosphate or the transition state analog GDP.AlF4-. Hydrogen bonding and steric interactions position Gln204 such that it interacts with a presumptive nucleophilic water molecule, but cannot interact with the pentacoordinate transition state. Gln204 must be released from this auto-inhibited state to participate in catalysis. RGS proteins may accelerate the rate of GTP hydrolysis by G protein alpha subunits, in part, by inserting an amino acid side chain into the site occupied by Gln204, thereby destabilizing the auto-inhibited state of Galpha.
  Selected figure(s)  
Figure 1.
Fig. 1. Electron density about the active site of the G[i 1]·GppNHp complex. The 1.5-Å 2 F[o] F[c] electron density map (blue) was calculated using SigmaA-weighted phases derived from the model, contoured at 1.5 . The model is shown as a ball-and-stick representation. Red, oxygen; yellow, carbon; blue, nitrogen; green, phosphorous; silver, magnesium. The figure was generated using the program BOBSCRIPT (51) and rendered with RASTER3D (52), and POVRAY.
Figure 2.
Fig. 2. The active site of G[i 1] in the (GTP analog) and (transition state analog·RGS4) bound complexes. Key features are labeled. A, G[i 1]·GppNHp; B, G[i 1]·GTP S; C, RGS4·G[i 1]·GDP·AlF[4]^ ·H[2]O; and D, hypothetical RGS4·G[i 1]·GppNHp complex. The main chain segments of G[i 1] are colored green (P-loop residues 38-48), blue (Switch I residues 178-184), and yellow (Switch II residues 200-208). The main chain segment of RGS4 in panels C and D is shown in red (residues 126-131). The atoms and water molecules are colored as described in Fig. 1, except that the phosphorous atoms are in yellow, magnesium is blue, and the sulfur atom of GTP S is green. In panel D, the region of the hypothetical model where Asn^128 of RGS4 and Gln^204 of G[i 1] collide is highlighted in cyan.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (1999, 274, 16669-16672) copyright 1999.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19427324 A.F.Neuwald (2009).
The charge-dipole pocket: a defining feature of signaling pathway GTPase on/off switches.
  J Mol Biol, 390, 142-153.  
18975915 A.Goc, T.E.Angel, B.Jastrzebska, B.Wang, P.L.Wintrode, and K.Palczewski (2008).
Different properties of the native and reconstituted heterotrimeric G protein transducin.
  Biochemistry, 47, 12409-12419.  
18258741 A.R.Zurita, and L.Birnbaumer (2008).
The same mutation in Gsalpha and transducin alpha reveals behavioral differences between these highly homologous G protein alpha-subunits.
  Proc Natl Acad Sci U S A, 105, 2363-2368.  
18940608 Z.Chen, W.D.Singer, S.M.Danesh, P.C.Sternweis, and S.R.Sprang (2008).
Recognition of the activated states of Galpha13 by the rgRGS domain of PDZRhoGEF.
  Structure, 16, 1532-1543.
PDB codes: 3cx6 3cx7 3cx8
17962409 A.F.Neuwald (2007).
Galpha Gbetagamma dissociation may be due to retraction of a buried lysine and disruption of an aromatic cluster by a GTP-sensing Arg Trp pair.
  Protein Sci, 16, 2570-2577.  
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
15653425 E.J.Helmreich (2004).
Structural flexibility of small GTPases. Can it explain their functional versatility?
  Biol Chem, 385, 1121-1136.  
15368366 M.V.Hinrichs, M.Montecino, M.Bunster, and J.Olate (2004).
Mutation of the highly conserved Arg165 and Glu168 residues of human Gsalpha disrupts the alphaD-alphaE loop and enhances basal GDP/GTP exchange rate.
  J Cell Biochem, 93, 409-417.  
12732734 S.Vorobiev, B.Strokopytov, D.G.Drubin, C.Frieden, S.Ono, J.Condeelis, P.A.Rubenstein, and S.C.Almo (2003).
The structure of nonvertebrate actin: implications for the ATP hydrolytic mechanism.
  Proc Natl Acad Sci U S A, 100, 5760-5765.
PDB codes: 1d4x 1nlv 1nm1 1nmd 1yag
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.  
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