Figure 9.
Structure analysis of AID mutations reveals altered substrate binding pocket of AIDR112H. (A) DDMut scores of selected mutations in AID. Red marks R112H mutation; black marks other AID mutations. (B) 3D models of WT and mutated AID (predicted) aligned together. (C) Structure of AID from RoseTTAFold aligned to AID crystal bound to dCMP (PDB: 5W0U). Catalytic residues H56, E58, C87, and C90, and the residue R112 highlighted. (D) Electrostatic surface potentials of WT AID and AIDR112H. Upper: whole protein; lower: catalytic pocket is zoomed in. Blue: positively charged residues; white: neutral residues; red: negatively charged residues. Position of primary catalytic residues H56, E58, C87, C90 together with R112 are highlighted. (E) Interatomic interactions of affected residues in WT AID and AIDR112H. (F) Interaction distance between W84 and H56 in WT AID and AIDR112H. Amino acids W84 and H56 are highlighted in purple. Green arrowheads highlight the interaction distance between the two highlighted amino acids. WT: 5.4–5.9 Å; AIDR112H: 3.7–3.9 Å. Refer to the image caption for details. Panel A: A bar graph comparing Gibbs Free Energy (delta G) values for selected mutations in AID. The horizontal axis lists different mutations, and the vertical axis shows Gibbs Free Energy values. The R112H mutation is marked in red, while other mutations are marked in black. Panel B: 3D models of wild type and mutated AID aligned together. The models show the structural changes due to mutations C87S, W80R, M139T, and R112H. Panel C: Structure of AID from RoseTTAFold aligned to AID crystal bound to dCMP. Catalytic residues H56, E58, C87, C90, and the residue R112 are highlighted. Panel D: Electrostatic surface potentials of wildtype AID and AIDR112H. The upper part shows the whole protein, and the lower part zooms in on the catalytic pocket. Blue indicates positively charged residues, white indicates neutral residues, and red indicates negatively charged residues. The positions of primary catalytic residues H56, E58, C87, C90, and R112 are highlighted. Panel E: Interatomic interactions of affected residues in wild type AID and AIDR112H. Panel F: Interaction distance between W84 and H56 in wild type AID and AIDR112H. Amino acids W84 and H56 are highlighted in purple. Green arrows highlight the interaction distance between the two highlighted amino acids. Wildtype interaction distance is 5.4 to 5.9, and AIDR112H interaction distance is 3.7 to 3.9.

Structure analysis of AID mutations reveals altered substrate binding pocket of AID R112H . (A) DDMut scores of selected mutations in AID. Red marks R112H mutation; black marks other AID mutations. (B) 3D models of WT and mutated AID (predicted) aligned together. (C) Structure of AID from RoseTTAFold aligned to AID crystal bound to dCMP (PDB: 5W0U). Catalytic residues H56, E58, C87, and C90, and the residue R112 highlighted. (D) Electrostatic surface potentials of WT AID and AIDR112H. Upper: whole protein; lower: catalytic pocket is zoomed in. Blue: positively charged residues; white: neutral residues; red: negatively charged residues. Position of primary catalytic residues H56, E58, C87, C90 together with R112 are highlighted. (E) Interatomic interactions of affected residues in WT AID and AIDR112H. (F) Interaction distance between W84 and H56 in WT AID and AIDR112H. Amino acids W84 and H56 are highlighted in purple. Green arrowheads highlight the interaction distance between the two highlighted amino acids. WT: 5.4–5.9 Å; AIDR112H: 3.7–3.9 Å.

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