Mechanism of tyrosine phosphorylation catalyzed by the insulin receptor tyrosine kinase: A semiempirical PM3 study

Fabio Pichierri, Yo Matsuo

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

The phosphorylation of tyrosine catalyzed by the tyrosine kinase domain of the insulin receptor has been investigated by means of semiempirical (PM3) molecular orbital calculations. A mechanism comprising ATP protonation followed by a proton shift within ATP and subsequent elimination-addition of the metaphosphate anion (PO3-) is proposed. Both the proton shift and elimination steps are endoergonic, with associated enthalpies of 17 and 18 kcal/mol, respectively. On the other hand, the addition of PO3- to tyrosine is exoergonic, with an associated enthalpy of 15 kcal/mol. Furthermore, the possible structural and catalytic roles of the two Mg2+ ions experimentally located in the active site of the insulin kinase domain have also been critically examined.

Original languageEnglish
Pages (from-to)257-267
Number of pages11
JournalJournal of Molecular Structure: THEOCHEM
Volume622
Issue number3
DOIs
Publication statusPublished - 2003 Mar 19
Externally publishedYes

Keywords

  • Enzymatic catalysis
  • Molecular orbital calculations
  • PM3
  • Phosphoryl transfer

ASJC Scopus subject areas

  • Biochemistry
  • Condensed Matter Physics
  • Physical and Theoretical Chemistry

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