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Figure 1 | BMC Bioinformatics

Figure 1

From: Characterization of pathogenic germline mutations in human Protein Kinases

Figure 1

Consensus model structure of summarizing the human Protein Kinase family The model structure of human Protein Kinase, based on MAP3K1, shows the basic two-lobe kinase fold, with the N- and C-terminal (green and orange respectively) lobes joined by a hinge region (magenta). Substrate recognition is through interaction with the activation segment (blue), a region in the C-terminal lobe. The substrate-binding groove is located between the catalytic loop, the P+1 loop (activation segment), helix D, helix F, helix G and helix H. ATP binds at a site between the two lobes (yellow) that includes five conserved residues: (i) Lysine 74 that interacts with the alpha and beta phosphates of ATP and thereby stabilizing it; (ii) a nearby glutamic acid (E96) forms a salt bridge with lysine 74 increasing the stabilization network; (iii) Aspartate 171 is the catalytic base that initiates phosphotransfer by deprotonating the acceptor serine, threonine or tyrosine; (iv) Asparagine 176 interacts with a secondary divalent cation, thereby positioning the gamma-phosphate of ATP, and finally (v) Aspartate 190 which chelates the primary divalent cation, indirectly positioning ATP at the same time.

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