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PDBsum entry 3gqi

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protein ligands metals Protein-protein interface(s) links
Transferase/transferase inhibitor PDB id
3gqi
Jmol
Contents
Protein chains
307 a.a. *
226 a.a. *
Ligands
DVT
ACP
Metals
_MG
Waters ×77
* Residue conservation analysis
PDB id:
3gqi
Name: Transferase/transferase inhibitor
Title: Crystal structure of activated receptor tyrosine kinase in c with substrates
Structure: Basic fibroblast growth factor receptor 1. Chain: a. Fragment: protein kinase domain. Synonym: fgfr-1, bfgf-r, fms-like tyrosine kinase 2, c-fgr. Engineered: yes. Mutation: yes. PhospholipasE C-gamma-1. Chain: b. Fragment: tandem sh2 domains.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: fgfbr, fgfr1, flg, flt2. Expressed in: escherichia coli. Expression_system_taxid: 562. Rattus norvegicus. Rat. Organism_taxid: 10116.
Resolution:
2.50Å     R-factor:   0.249     R-free:   0.289
Authors: J.H.Bae,E.D.Lew,S.Yuzawa,F.Tome,I.Lax,J.Schlessinger
Key ref: J.H.Bae et al. (2009). The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site. Cell, 138, 514-524. PubMed id: 19665973
Date:
24-Mar-09     Release date:   18-Aug-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P11362  (FGFR1_HUMAN) -  Fibroblast growth factor receptor 1
Seq:
Struc:
 
Seq:
Struc:
822 a.a.
307 a.a.*
Protein chain
Pfam   ArchSchema ?
P10686  (PLCG1_RAT) -  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1290 a.a.
226 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 1: Chain A: E.C.2.7.10.1  - Receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
ATP
+ [protein]-L-tyrosine
=
ADP
Bound ligand (Het Group name = ACP)
matches with 81.25% similarity
+ [protein]-L-tyrosine phosphate
   Enzyme class 2: Chain B: E.C.3.1.4.11  - Phosphoinositide phospholipase C.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
      Reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
+ H(2)O
= 1D-myo-inositol 1,4,5-trisphosphate
+ diacylglycerol
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     intracellular signal transduction   6 terms 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     7 terms  

 

 
    reference    
 
 
Cell 138:514-524 (2009)
PubMed id: 19665973  
 
 
The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site.
J.H.Bae, E.D.Lew, S.Yuzawa, F.Tomé, I.Lax, J.Schlessinger.
 
  ABSTRACT  
 
SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. However, the modest binding affinity of SH2 domains to pY containing peptides may not account for and likely represents an oversimplified mechanism for regulation of selectivity of signaling pathways in living cells. Here we describe the crystal structure of the activated tyrosine kinase domain of FGFR1 in complex with a phospholipase Cgamma fragment. The structural and biochemical data and experiments with cultured cells show that the selectivity of phospholipase Cgamma binding and signaling via activated FGFR1 are determined by interactions between a secondary binding site on an SH2 domain and a region in FGFR1 kinase domain in a phosphorylation independent manner. These experiments reveal a mechanism for how SH2 domain selectivity is regulated in vivo to mediate a specific cellular process.