4W9X

Crystal Structure of BMP-2-inducible kinase in complex with baricitinib

Summary for 4W9X

• Entry DOI: 10.2210/pdb4w9x/pdb
• Related: 4W9W
• Descriptor: BMP-2-inducible protein kinase, 1,2-ETHANEDIOL, Baricitinib, ... (4 entities in total)
• Functional Keywords: kinase, small-molecule, catalytic domain, protein binding, inhibitor, structural genomics, structural genomics consortium, sgc, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : Q9NSY1
• Total number of polymer chains: 1
• Total formula weight: 35286.59

Authors

Sorrell, F.J.,Elkins, J.M.,Krojer, T.,Williams, E.,Savitsky, P.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2014-08-28, release date: 2014-09-10, Last modification date: 2024-05-08)

Primary citation

Sorrell, F.J.,Szklarz, M.,Abdul Azeez, K.R.,Elkins, J.M.,Knapp, S.
Family-wide Structural Analysis of Human Numb-Associated Protein Kinases.
Structure, 24:401-411, 2016

PubMed 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.

PubMed: 26853940
DOI: 10.1016/j.str.2015.12.015

Experimental method

X-RAY DIFFRACTION (2.14 Å)