Structural features that specify tyrosine kinase activity deduced from homology modeling of the epidermal growth factor receptor.

AUTOR(ES)

Knighton, D R

RESUMO

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.

Documentos Relacionados

• Tyrosine kinase activity is essential for the association of phospholipase C-gamma with the epidermal growth factor receptor.
• Tumor promoters block tyrosine-specific phosphorylation of the epidermal growth factor receptor.
• A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains.
• Epidermal growth factor (EGF) stimulates association and kinase activity of Raf-1 with the EGF receptor.
• Signal transduction by the epidermal growth factor receptor after functional desensitization of the receptor tyrosine protein kinase activity.