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Fig. 3 | Cell & Bioscience

Fig. 3

From: AKT inhibition in the central nervous system induces signaling defects resulting in psychiatric symptomatology

Fig. 3

Modeling the Q61H mutation onto the crystal structure of the Akt1 PH domain. A The structure of the Akt1 PH domain in complex with Ins(1,3,4,5)-tetrakisphosphate [1h10.pdb]. The ribbon structure is rainbow colored, from blue at the N-terminus to red on the C-terminal helix (res: 93–114). The bound Ins(1,3,4,5)-tetrakisphosphate is shown with a molecular surface. Key side chain residues Q61, R76, and D85 are displayed as sticks, where Q61 is highlighted in magenta. B Amino acid homology comparison between human Akt1, Akt2, and Akt3 kinases. Key side chain residues of Akt3 Q60, R75, E84 (Akt1 and Akt2 Q61, R76, E85) are indicated. C Zoom-in view of the crystallographic conformation of Q61, R76, and E85, where a strong salt bridge electrostatic interaction is formed between R76 and E85. D An alternative conformation of the Q61 side chain from 100 ps molecular dynamics simulation of the PH domain. This alternative conformation illustrates how the carbonyl group of the Q61 side chain is able to form favorable side chain interactions with R76. The hydrogen bonding interaction shown with a green dashed line is characterized by a 2.74 Å distance (between Q61@OE1 and R76@NH1). E. Modeled low-energy conformation of the Q61H mutation into the crystallographic conformation

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