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Updated: Mar 26, 2026

Nuclear Magnetic Resonance Spectroscopy for the Identification of Multiple Phosphorylations of Intrinsically Disordered Proteins
Published on: December 27, 2016
Family-wide Structural Analysis of Human Numb-Associated Protein Kinases
Fiona J Sorrell1, Marta Szklarz1, Kamal R Abdul Azeez1
1Nuffield Department of Clinical Medicine, Structural Genomics Consortium and Target Discovery Institute (TDI), University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.
Abstract:
The highly diverse Numb-associated kinase (NAK) family has been linked to broad cellular functions including receptor-mediated endocytosis, Notch pathway modulation, osteoblast differentiation, and dendrite morphogenesis. Consequently, NAK kinases play a key role in a diverse range of diseases from Parkinson's and prostate cancer to HIV. Due to the plasticity of this kinase family, NAK kinases are often inhibited by approved or investigational drugs and have been associated with side effects, but they are also potential drug targets. The presence of cysteine residues in some NAK family members provides the possibility for selective targeting via covalent inhibition. Here we report the first high-resolution structures of kinases AAK1 and BIKE in complex with two drug candidates. The presented data allow a comprehensive structural characterization of the NAK kinase family and provide the basis for rational design of selective NAK inhibitors.
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