Open AccessStructural features that specify tyrosine kinase activity deduced from homology modeling of the epidermal growth factor receptor.
Author(s) -
Daniel R. Knighton,
Deborah L. Cadena,
Jie Zheng,
Lynn F. Ten Eyck,
Susan S. Taylor,
Janusz M. Sowadski,
Gordon N. Gill
Publication year - 1993
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.90.11.5001
Subject(s) - sh3 domain , biochemistry , biology , proto oncogene tyrosine protein kinase src , tyrosine kinase , epidermal growth factor , receptor tyrosine kinase , c raf , kinase , chemistry , protein kinase a , mitogen activated protein kinase kinase , signal transduction , receptor
To identify structural features that distinguish protein-tyrosine kinases from protein-serine kinases, a molecular model of the kinase domain of epidermal growth factor receptor was constructed by substituting its amino acid sequence for the amino acid sequence of the catalytic subunit of cAMP-dependent protein kinase in a 2.7-A refined crystallographic model. General folding was conserved as was the configuration of invariant residues at the active site. Two sequence motifs that distinguish the two families correspond to loops that converge at the active site of the enzyme. A conserved arginine in the catalytic loop is proposed to interact with the gamma phosphate of ATP. The second loop provides a binding surface that positions the tyrosine of the substrate. A positively charged surface provides additional sites for substrate recognition.