Related Experiment Video

Updated: Aug 15, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

Crystal structures of active SRC kinase domain complexes

Christine B Breitenlechner1, Norman A Kairies, Konrad Honold

  • 1Abteilung Strukturforschung, Max-Planck-Institut für Biochemie, 82152 Martinsried, Germany.

Journal of Molecular Biology
|September 20, 2005
PubMed

Insights

Structural studies reveal active c-Src kinase domain dynamics. New crystal structures show how inhibiting this proto-oncoprotein involves flexible conformations and specific ligand interactions, crucial for drug discovery.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Drug Discovery

Background:

  • c-Src is a proto-oncoprotein and a key target in drug discovery.
  • Inactive c-Src structures reveal rigid, assembled conformations.
  • Limited structural data exists for active, flexible c-Src forms.

Purpose of the Study:

  • To determine the structural basis of active c-Src kinase domain conformations.
  • To investigate ligand binding in active c-Src.
  • To provide insights into c-Src drug development.

Main Methods:

  • X-ray crystallography
  • Analysis of apo and ligand-bound c-Src kinase domain structures
  • High-resolution structural determination (1.95Å–2.9Å)

Main Results:

  • Three crystal structures of dimeric active c-Src kinase domain were determined.
  • Active c-Src adopts a more open and flexible conformation compared to inactive states.
  • Specific interactions of ATP-site inhibitors CGP77675 and purvalanol A with c-Src were elucidated.

Conclusions:

  • The active c-Src kinase domain exhibits flexibility independent of interdomain interactions.
  • Ligand binding reveals specific interactions, including with c-Src residue Threonine 340.
  • Structural insights advance understanding of c-Src regulation and inform targeted drug design.

More Related Videos

Modeling an Enzyme Active Site using Molecular Visualization Freeware14:37

Modeling an Enzyme Active Site using Molecular Visualization Freeware

Published on: December 25, 2021

Related Concept Videos

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...