A quantum mechanical study on phosphotyrosyl peptide binding to the SH2 domain of p56lck tyrosine kinase with insights into the biochemistry of intracellular signal transduction events

研究成果: Article査読

10 被引用数 (Scopus)

抄録

A study on the interaction between a phosphotyrosyl peptide with the SH2 domain of Lck kinase has been undertaken with the aid of semiempirical linear-scaling quantum mechanical methods. The structure of this complex has been solved at atomic resolution and, hence, it represents the ideal candidate for studying the charge deformation effects induced by the phosphopeptide on the binding site. Substantial changes in the charge of amino acid residues located in the binding pocket of the protein are observed upon ligand binding. More specifically, our quantum chemical calculations indicate that H-bonds involving charged side-chains are subject to consistent charge deformation effects whereas those forming salt bridges are unaffected by ligand binding. Furthermore, ligand binding has the effect of changing both the magnitude and direction of the protein's macrodipole, which rotates approximately 150°with respect that of the unliganded protein. This suggests that a change in the polarization state of the protein might acts as a switch during the transmission of intracellular signals. The binding energy calculated with the aid of the COSMO solvation model corresponds to about -200 kcal/mol, most of which is attributed to the interaction of the phosphotyrosine head with the amino acid chains located in the binding site of the SH2 domain.

本文言語English
ページ(範囲)295-304
ページ数10
ジャーナルBiophysical Chemistry
109
2
DOI
出版ステータスPublished - 2004 5 1

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 有機化学

フィンガープリント

「A quantum mechanical study on phosphotyrosyl peptide binding to the SH2 domain of p56<sup>lck</sup> tyrosine kinase with insights into the biochemistry of intracellular signal transduction events」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル