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PDBsum entry 2rgb

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protein ligands metals links
Oncoprotein PDB id
2rgb
Jmol
Contents
Protein chain
166 a.a. *
Ligands
GNP
Metals
_CA
_MG ×2
Waters ×196
* Residue conservation analysis
PDB id:
2rgb
Name: Oncoprotein
Title: Crystal structure of h-rasq61k-gppnhp
Structure: Gtpase hras. Chain: a. Fragment: residues 1-166. Synonym: transforming protein p21, p21ras, h-ras-1, c-h- ras, ha-ras. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hras, hras1. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Resolution:
1.35Å     R-factor:   0.200     R-free:   0.218
Authors: G.Buhrman,G.Wink,C.Mattos
Key ref:
G.Buhrman et al. (2007). Transformation efficiency of RasQ61 mutants linked to structural features of the switch regions in the presence of Raf. Structure, 15, 1618-1629. PubMed id: 18073111 DOI: 10.1016/j.str.2007.10.011
Date:
03-Oct-07     Release date:   18-Dec-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01112  (RASH_HUMAN) -  GTPase HRas
Seq:
Struc:
189 a.a.
166 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     membrane   1 term 
  Biological process     signal transduction   3 terms 
  Biochemical function     GTP binding     1 term  

 

 
DOI no: 10.1016/j.str.2007.10.011 Structure 15:1618-1629 (2007)
PubMed id: 18073111  
 
 
Transformation efficiency of RasQ61 mutants linked to structural features of the switch regions in the presence of Raf.
G.Buhrman, G.Wink, C.Mattos.
 
  ABSTRACT  
 
Transformation efficiencies of Ras mutants at residue 61 range over three orders of magnitude, but the in vitro GTPase activity decreases 10-fold for all mutants. We show that Raf impairs the GTPase activity of RasQ61L, suggesting that the Ras/Raf complex differentially modulates transformation. Our crystal structures show that, in transforming mutants, switch II takes part in a network of hydrophobic interactions burying the nucleotide and precatalytic water molecule. Our results suggest that Y32 and a water molecule bridging it to the gamma-phosphate in the wild-type structure play a role in GTP hydrolysis in lieu of the Arg finger in the absence of GAP. The bridging water molecule is absent in the transforming mutants, contributing to the burying of the nucleotide. We propose a mechanism for intrinsic hydrolysis in Raf-bound Ras and elucidate structural features in the Q61 mutants that correlate with their potency to transform cells.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. Active Site Surfaces in the RasQ61 Mutants and in the Wild-Type Structure in Complex with GppNHp
(A–F) (A) Q61L; (B) Q61V; (C) Q61K; (D) Q61I (R32); (E) Q61G (PDB code: 1ZW6); (F) wild-type (R32). Surfaces were constructed by using PyMOL and were colored based on atom type (N, blue; O, red; C, green). Only protein atoms were used to define the surface. Areas outlined in white define the protein/solvent interface. Wat175 represents the precatalytic water molecule.
Figure 5.
Figure 5. Switch I in the Wild-Type and Mutant Ras Structures: Comparisons with Biologically Relevant Complexes
(A) Wild-type Ras-GppNHp (green, with water molecules in red) and Raps-GppNHp/Raf-RBD (yellow, with water molecules in orange).
(B) RasQ61L-GppNHp (green, with water molecules in red) and Ran-GppNHp-importin-β (yellow, with water molecules in orange). The nucleotide is in gray. Red, dashed lines represent hydrogen bonds.
 
  The above figures are reprinted from an Open Access publication published by Cell Press: Structure (2007, 15, 1618-1629) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20949621 L.Gremer, T.Merbitz-Zahradnik, R.Dvorsky, I.C.Cirstea, C.P.Kratz, M.Zenker, A.Wittinghofer, and M.R.Ahmadian (2011).
Germline KRAS mutations cause aberrant biochemical and physical properties leading to developmental disorders.
  Hum Mutat, 32, 33-43.  
19603018 F.Loupakis, A.Ruzzo, C.Cremolini, B.Vincenzi, L.Salvatore, D.Santini, G.Masi, I.Stasi, E.Canestrari, E.Rulli, I.Floriani, K.Bencardino, N.Galluccio, V.Catalano, G.Tonini, M.Magnani, G.Fontanini, F.Basolo, A.Falcone, and F.Graziano (2009).
KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer.
  Br J Cancer, 101, 715-721.  
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.