3CD3

Crystal structure of phosphorylated human feline sarcoma viral oncogene homologue (v-FES) in complex with staurosporine and a consensus peptide

Summary for 3CD3

• Entry DOI: 10.2210/pdb3cd3/pdb
• Related: 3CBL
• Descriptor: Proto-oncogene tyrosine-protein kinase Fes/Fps, Synthetic peptide, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: fes, v-fes, fujinami, avian sarcoma, viral, oncogene, feline sarcoma virus, active, sgc, structural genomics consortium, atp-binding, kinase, nucleotide-binding, phosphoprotein, proto-oncogene, sh2 domain, transferase, tyrosine-protein kinase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 44958.26

Authors

Filippakopoulos, P.,Salah, E.,Cooper, C.,Picaud, S.S.,Elkins, J.M.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Weigelt, J.,Bountra, C.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2008-02-26, release date: 2008-03-25, Last modification date: 2024-11-06)

Primary citation

Filippakopoulos, P.,Kofler, M.,Hantschel, O.,Gish, G.D.,Grebien, F.,Salah, E.,Neudecker, P.,Kay, L.E.,Turk, B.E.,Superti-Furga, G.,Pawson, T.,Knapp, S.
Structural Coupling of SH2-Kinase Domains Links Fes and Abl Substrate Recognition and Kinase Activation
Cell(Cambridge,Mass.), 134:793-803, 2008

PubMed Abstract: The SH2 domain of cytoplasmic tyrosine kinases can enhance catalytic activity and substrate recognition, but the molecular mechanisms by which this is achieved are poorly understood. We have solved the structure of the prototypic SH2-kinase unit of the human Fes tyrosine kinase, which appears specialized for positive signaling. In its active conformation, the SH2 domain tightly interacts with the kinase N-terminal lobe and positions the kinase alphaC helix in an active configuration through essential packing and electrostatic interactions. This interaction is stabilized by ligand binding to the SH2 domain. Our data indicate that Fes kinase activation is closely coupled to substrate recognition through cooperative SH2-kinase-substrate interactions. Similarly, we find that the SH2 domain of the active Abl kinase stimulates catalytic activity and substrate phosphorylation through a distinct SH2-kinase interface. Thus, the SH2 and catalytic domains of active Fes and Abl pro-oncogenic kinases form integrated structures essential for effective tyrosine kinase signaling.

PubMed: 18775312
DOI: 10.1016/j.cell.2008.07.047

Experimental method

X-RAY DIFFRACTION (1.98 Å)