Fig. 5
From: Global redox proteome and phosphoproteome analysis reveals redox switch in Akt
MD simulations predict the C60-C77 disulfide in Akt increases PIP3 affinity. a Akt1 PH domain (1unp) showing the disulfide bond between C60 and C77, the key residues required for PIP3 binding and loops 1 to 3. b Comparison of the Akt1 crystal structure 1unp (transparent) with the WT and c C60/C77S structures obtained after ~100 ns MD. d Time series of the E17(O)-R86(N) distance in WT and mutant Akt1. Only the distance between the closest O-N atoms are shown. e Time series of the Ca-Ca distances between the residues E17 in loop 1, and R86 in loop 3 in WT and mutant Akt1. f–h Comparison of the backbone RMSDs of the three loops in WT and mutant Akt1 calculated using the crystal structure as a reference. For loop 1, the RMSD is calculated for the residues 12–26, which are involved in binding of PIP3. i Residue specific RMSDs of the loop 1 residues 12–26 for the WT and C60/77S and protonated C60/77 mutant Akts. j–l Time series of the contact distances involved in PIP3 binding to WT Akt (blue) and Akt-C60/77/S (red). j WT Akt K14(NZ)–PIP3 (OPG/H) and Akt-C60/77S K14(NZ)–PIP3 (OPH). k WT Akt R25(N2)–PIP3 (O5P/O6P) and Akt-C60/77S R25(N2)–PIP3 (OPG). l WT Akt N53(ND2)–PIP3 (O6P/O8P) and Akt-C60/77S K14(ND2)–PIP3 (O8P). m Snapshots of WT (left-hand panels) and mutant (right-hand panels) Akt1-PIP3 complex at 0 and 50 ns.
