KinaseDomäne

KinaseDomäne is a conserved protein domain that constitutes the catalytic core of many protein kinases. It mediates the transfer of a phosphate group from ATP to substrate proteins, thereby modulating their activity, interactions, or localization. The domain is typically about 250 to 300 amino acids long and functions within a larger, multi-domain kinase.

Structurally, KinaseDomäne comprises two lobes: an N-lobe rich in beta-sheets and a C-lobe rich in alpha-helices. The ATP-binding pocket lies in the cleft between the two lobes. Conserved motifs define the catalytic mechanism, including the glycine-rich loop in subdomain I, the VAIK motif in subdomain II that coordinates ATP, the DFG motif at the start of the activation loop, and the HRD motif in the catalytic loop. Phosphorylation of the activation loop or other regulatory sites induces conformational changes that switch the domain between active and inactive states.

KinaseDomäne activity targets serine, threonine, or tyrosine residues and is regulated by regulatory domains, scaffolding proteins, lipids, and phosphorylation. In many kinases, the domain is part of a larger multidomain protein that integrates stimulus sensing with catalytic output. Pseudokinases retain a kinase-like KinaseDomäne but lack catalytic activity and often regulate signaling by non-catalytic means.

The KinaseDomäne is a major target in drug discovery, with inhibitors designed to bind the ATP pocket or to target allosteric sites, especially in cancer and metabolic diseases. Understanding its structure and regulation is central to decoding phosphorylation signaling networks.