PMID- 9219684
OWN - NLM
STAT- MEDLINE
DCOM- 19980323
LR  - 20220408
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 277
IP  - 5324
DP  - 1997 Jul 18
TI  - The Ras-RasGAP complex: structural basis for GTPase activation and its loss in 
      oncogenic Ras mutants.
PG  - 333-8
AB  - The three-dimensional structure of the complex between human H-Ras bound to 
      guanosine diphosphate and the guanosine triphosphatase (GTPase)-activating domain 
      of the human GTPase-activating protein p120GAP (GAP-334) in the presence of 
      aluminum fluoride was solved at a resolution of 2.5 angstroms. The structure 
      shows the partly hydrophilic and partly hydrophobic nature of the communication 
      between the two molecules, which explains the sensitivity of the interaction 
      toward both salts and lipids. An arginine side chain (arginine-789) of GAP-334 is 
      supplied into the active site of Ras to neutralize developing charges in the 
      transition state. The switch II region of Ras is stabilized by GAP-334, thus 
      allowing glutamine-61 of Ras, mutation of which activates the oncogenic 
      potential, to participate in catalysis. The structural arrangement in the active 
      site is consistent with a mostly associative mechanism of phosphoryl transfer and 
      provides an explanation for the activation of Ras by glycine-12 and glutamine-61 
      mutations. Glycine-12 in the transition state mimic is within van der Waals 
      distance of both arginine-789 of GAP-334 and glutamine-61 of Ras, and even its 
      mutation to alanine would disturb the arrangements of residues in the transition 
      state.
FAU - Scheffzek, K
AU  - Scheffzek K
AD  - Max-Planck-Institut fur molekulare Physiologie, Abteilung Strukturelle Biologie, 
      Rheinlanddamm 201, 44139 Dortmund, Germany.
FAU - Ahmadian, M R
AU  - Ahmadian MR
FAU - Kabsch, W
AU  - Kabsch W
FAU - Wiesmuller, L
AU  - Wiesmuller L
FAU - Lautwein, A
AU  - Lautwein A
FAU - Schmitz, F
AU  - Schmitz F
FAU - Wittinghofer, A
AU  - Wittinghofer A
LA  - eng
SI  - PDB/1WQ1
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Aluminum Compounds)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Proteins)
RN  - 0 (ras GTPase-Activating Proteins)
RN  - 146-91-8 (Guanosine Diphosphate)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ras Proteins)
RN  - Q80VPU408O (Fluorides)
RN  - Z77H3IKW94 (aluminum fluoride)
SB  - IM
CIN - Science. 1997 Jul 18;277(5324):329-30. PMID: 9518363
MH  - Aluminum Compounds/chemistry/metabolism
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Catalysis
MH  - Cell Transformation, Neoplastic
MH  - Crystallography, X-Ray
MH  - Enzyme Activation
MH  - Fluorides/chemistry/metabolism
MH  - GTP Phosphohydrolases/chemistry/*metabolism
MH  - GTP-Binding Proteins/chemistry/metabolism
MH  - GTPase-Activating Proteins
MH  - Guanosine Diphosphate/metabolism
MH  - Guanosine Triphosphate/metabolism
MH  - Humans
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutation
MH  - *Protein Conformation
MH  - Protein Structure, Secondary
MH  - Proteins/*chemistry/*metabolism
MH  - Signal Transduction
MH  - ras GTPase-Activating Proteins
MH  - ras Proteins/chemistry/genetics/*metabolism
EDAT- 1997/07/18 00:00
MHDA- 1997/07/18 00:01
CRDT- 1997/07/18 00:00
PHST- 1997/07/18 00:00 [pubmed]
PHST- 1997/07/18 00:01 [medline]
PHST- 1997/07/18 00:00 [entrez]
AID - 10.1126/science.277.5324.333 [doi]
PST - ppublish
SO  - Science. 1997 Jul 18;277(5324):333-8. doi: 10.1126/science.277.5324.333.