AlphaFold2 models of the active form of all 437 catalytically competent human protein kinase domains.

ABSTRACT: Humans have 437 catalytically competent protein kinase domains with the typical kinase fold, similar to the structure of Protein Kinase A (PKA). Only 155 of these kinases are in the Protein Data Bank in their active form. The active form of a kinase must satisfy requirements for binding ATP, magnesium, and substrate. From structural bioinformatics analysis of 40 unique substrate-bound kinases, we derived several criteria for the active form of protein kinases. We include requirements on the DFG motif of the activation loop but also on the positions of the N-terminal and C-terminal segments of the activation loop that must be placed appropriately to bind substrate. Because the active form of catalytic kinases is needed for understanding substrate specificity and the effects of mutations on

SUBMITTER: Faezov B 

PROVIDER: S-EPMC10401967 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature