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 language | English |
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Pages (from-to) | 257-267 |
Number of pages | 11 |
Journal | Journal of Molecular Structure: THEOCHEM |
Volume | 622 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2003 Mar 19 |
Externally published | Yes |
Keywords
- Enzymatic catalysis
- Molecular orbital calculations
- PM3
- Phosphoryl transfer
ASJC Scopus subject areas
- Biochemistry
- Condensed Matter Physics
- Physical and Theoretical Chemistry