3D structure of the kinase domain of Activin receptor1 (Acvr1) complex with inhibitor shows with the protein including a and a [1]. Water molecule is shown as red sphere.
Rabbit [2]. Water molecules are shown as red spheres.
The structure of the complex between M-CSF and its receptor shows that a . There are [3]. .
The via the conserved kinase DFG motif (colored in salmon) and its gatekeeper threonine residue (colored in magenta)[4].
Lapatinib is a EGFR inhibitor used in breast cancer treatment. EGFRs are overexpressed in many types of human carcinomas including lung, pancreatic, and breast cancer, and are often mutated. This overexpression leads to excessive activation of the anti-apoptotic Ras signaling cascade, resulting in uncontrolled DNA synthesis and cell proliferation. The is responsible for activating this Ras signaling cascade. Upon binding ligands like Epidermal Growth Factor, EGFR dimerizes and autophosphorylates several tyrosine residues at its C-terminal domain. Upon phosphorylation, EGFR undergoes a significant conformational shift, revealing an additional binding site capable of binding and activating downstream signaling proteins.
Gefitinib inhibits the EGFR by located within the kinase domain. Residues Lys745, Leu788, Ala743, Thr790, Gln791, Met193, Pro794, Gly796, Asp800, Ser719, Glu762, & Met766 tightly bind the inhibitor. Unable to bind ATP, EGFR is incapable of autophosphorylating its C-terminal tyrosines, and the uncontrolled cell-proliferation signal is terminated.
Erlotinib inhibits the EGFR by located within the kinase domain. EGFR uses residues Asp831, Lys721, Thr766, Leu820, Gly772, Phe771, Leu694, Pro770, Met769, Leu768, Gln767 & Ala719 to tightly bind the inhibitor. Unable to bind ATP, EGFR is incapable of autophosphorylating its C-terminal tyrosines, and the uncontrolled cell-proliferation signal is terminated.
See also Herceptin - Mechanism of Action
Ephrins (Eph) are the membrane-bound ligands of ephrin receptors. The binding of Eph and ephrin receptors is achieved via cell-cell interaction. Eph/Eph receptor signaling regulates embryonic development, guidance of axon growth, long-term potentiation, angiogenesis and stem-cell differentiation [5]. Eph-A5 is implicated in spinal cord injury. Eph-A1 is implicated in myocardial injury and renal reperfusion injury. (PDB code 3mx0).[6]
. Water molecules are shown as red spheres.
.
(3fxx).[7]
See also:
