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Catalytic Site Atlas

CSA LITERATURE entry for 1ir3

E.C. namereceptor protein-tyrosine kinase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz)
CSA Homologues of 1ir3There are 1415 Homologs
CSA Entries With UniProtID P06213
CSA Entries With EC Number
PDBe Entry 1ir3
PDBSum Entry 1ir3
MACiE Entry M0246

Literature Report

IntroductionPhosphorylated insulin receptor tyrosine kinase from Homo sapiens catalyses the phosphorylation of Tyr on intracellular proteins that are related to the STATK pathway. The phosphoryl group is transferred from ATP to form ADP. On carrying out this function, the enzyme activates the signalling cascade inside the cell.
Mechansim1. Asp 1132 deprotonates the substrate Tyr hydroxide, activating it for nucleophilic attack on the gamma phosphate of ATP, which forms a pentavalent transition state. 2. The transition state is stabilised by hydrogen bonding to Arg 1136. 3. The leaving group is protonated by the protonated Asp 1132, assisted by the interaction of Mg2+ 301 which serves to make the oxygen lone pair more available for protonation.

Catalytic Sites for 1ir3

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA11321159macie:sideChainActs as a general base to deprotonate the Tyr residue hydroxide of the substrate, activating it for nucleophilic attack.
ArgA11361163macie:sideChainHydrogen bonds to the negatively charged oxygen of the gamma phosphate, stabilising the transition state.

Literature References

Notes:It is still a matter of debate whether Asp 1132 deprotonates the Tyr residue of the substrate or whether it just hydrogen bonds to it, thereby activating it for nucleophilic attack.
F. Pichierri
Mechanism of tyrosine phosphorylation catalyzed by the insulin receptor tyrosine kinase: a semiempirical PM3 study
J. Mol. Struct. (Theochem) 2003 622 257-267
PubMed: Pichierri2003