Role of phosphorylated Thr-197 in the catalytic subunit of cAMP-dependent protein kinase
Protein phosphorylation of Thr-197 in the activation loop of the catalytic subunit (C-subunit) of cAMP-dependent protein kinase (PKA) is an essential step for its proper biological function. In order to explore the influences triggered by phosphoryiation of Thr-197, comparative molecular dynamics (MD) simulation studies with or without phosphate group on Thr-197 and Ser-338 were performed on the complex of C-subunit bound to ATP and two Mg2+ ions C/Mg2ATP complex) and on the complex of C-subunit bound to substrate peptide (C/substrate complex). The results present a decreased flexibility of the activation loop in the phosphorylated state, because of several critical interactions formed by the phosphorylated Thr-197 with His-87, Arg-165, Lys-189 and Thr-195. The unphosphorylated activation loop does not block the substrate-binding site, which is in good agreement with experimental result. In unphos phorylated state, the crucial interaction between Thr-197and His-87 of C-helix does not exist, which eventually makes glycine-rich loop run away from its original position and displaces the phosphates group of ATP. We suggest that the reduction in rate of phosphoryl transfer may be caused by the displacement of γ-phosphate group that demolish phosphoryl transfer in-line mechanism,
cAMP-dependent protein kinase Thr-137 Ptosphoryiation Molecular dynamics simulation Phosphoryl transfer
Hai-Xiao Jin Tian-Xing Wu Yong-Jun Jiang Jian-Wei Zou Shu-Lin Zhuang Xiang Mao Qing-Sen Yu
Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China;Ningbo Institute of Technolo Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China Ningbo Institute of Technology, Zhejiang University, Ningbo 315104, PR China Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas H
国际会议
杭州
英文
1316-1322
2007-04-01（万方平台首次上网日期，不代表论文的发表时间）