PDBsum entry 1a4r

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Hydrolase PDB id
Protein chains
190 a.a. *
Waters ×54
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: G12v mutant of human placental cdc42 gtpase in the gdp form
Structure: G25k gtp-binding protein. Chain: a, b. Synonym: g25k, cdc42 homolog. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Tissue: placenta. Cellular_location: cytoplasm, inner side of membrane. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PQS)
2.50Å     R-factor:   0.228     R-free:   0.280
Authors: M.G.Rudolph,I.R.Vetter,A.Wittinghofer
Key ref: M.G.Rudolph et al. (1999). Nucleotide binding to the G12V-mutant of Cdc42 investigated by X-ray diffraction and fluorescence spectroscopy: two different nucleotide states in one crystal. Protein Sci, 8, 778-787. PubMed id: 10211824 DOI: 10.1110/ps.8.4.778
02-Feb-98     Release date:   02-Mar-99    
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Protein chains
Pfam   ArchSchema ?
P60953  (CDC42_HUMAN) -  Cell division control protein 42 homolog
191 a.a.
190 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   24 terms 
  Biological process     cardiac conduction system development   70 terms 
  Biochemical function     nucleotide binding     10 terms  


DOI no: 10.1110/ps.8.4.778 Protein Sci 8:778-787 (1999)
PubMed id: 10211824  
Nucleotide binding to the G12V-mutant of Cdc42 investigated by X-ray diffraction and fluorescence spectroscopy: two different nucleotide states in one crystal.
M.G.Rudolph, A.Wittinghofer, I.R.Vetter.
The 2.5 A crystal structure of the full length human placental isoform of the Gly12 to Val mutant Cdc42 protein (Cdc42(G12V)) bound to both GDP/Mg2+ and GDPNH2 (guanosine-5'-diphospho-beta-amidate) is reported. The crystal contains two molecules in the asymmetric unit, of which one has bound GDP/Mg2+, while the other has bound GDPNH2 without a Mg2+ ion. Crystallization of the protein was induced via hydrolysis of the Cdc42 x GppNHp complex by the presence of contaminating alkaline phosphatase activity in combination with the crystallization conditions. This prompted us to compare the binding characteristics of GDPNH2 vs. GDP. The amino group of GDPNH2 drastically reduces the affinity to Cdc42 in comparison with that of GDP, causes the loss of the Mg2+ ion, and apparently also increases the conformational flexibility of the protein as seen in the crystal. Both the switch I and switch II regions are visible in the electron density of the GDP-bound molecule, but not in the molecule bound to GDPNH2. The C-terminus containing the CaaX-motif is partly ordered in both molecules due to an intramolecular disulfide bond formed between Cys105/Cys188 and Cys305/Cys388, respectively.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19745154 J.Yang, Z.Zhang, S.M.Roe, C.J.Marshall, and D.Barford (2009).
Activation of Rho GTPases by DOCK exchange factors is mediated by a nucleotide sensor.
  Science, 325, 1398-1402.
PDB codes: 2wm9 2wmn 2wmo
18348980 M.J.Phillips, G.Calero, B.Chan, S.Ramachandran, and R.A.Cerione (2008).
Effector proteins exert an important influence on the signaling-active state of the small GTPase Cdc42.
  J Biol Chem, 283, 14153-14164.
PDB code: 2qrz
16428446 D.M.Truckses, J.E.Bloomekatz, and J.Thorner (2006).
The RA domain of Ste50 adaptor protein is required for delivery of Ste11 to the plasma membrane in the filamentous growth signaling pathway of the yeast Saccharomyces cerevisiae.
  Mol Cell Biol, 26, 912-928.  
12777804 K.Longenecker, P.Read, S.K.Lin, A.P.Somlyo, R.K.Nakamoto, and Z.S.Derewenda (2003).
Structure of a constitutively activated RhoA mutant (Q63L) at 1.55 A resolution.
  Acta Crystallogr D Biol Crystallogr, 59, 876-880.
PDB code: 1kmq
12093730 G.Buchwald, A.Friebel, J.E.Galán, W.D.Hardt, A.Wittinghofer, and K.Scheffzek (2002).
Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE.
  EMBO J, 21, 3286-3295.
PDB code: 1gzs
11438672 G.Buchwald, E.Hostinova, M.G.Rudolph, A.Kraemer, A.Sickmann, H.E.Meyer, K.Scheffzek, and A.Wittinghofer (2001).
Conformational switch and role of phosphorylation in PAK activation.
  Mol Cell Biol, 21, 5179-5189.  
11113198 H.U.Mösch, T.Köhler, and G.H.Braus (2001).
Different domains of the essential GTPase Cdc42p required for growth and development of Saccharomyces cerevisiae.
  Mol Cell Biol, 21, 235-248.  
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