Fig. 5: Mechanism of AcuC inhibition by AcuB and its regulation via Ap4A.
From: A protein adaptor mediating Ap4A-dependent control of protein acetylation
a Structural alignment of the overall structure and catalytic center of (Gt)AcuC (cyan, AlphaFold 3) with (Hs)HDAC1 (magenta, PDB ID: 4BKX), (Hs)HDAC2 (grey, PDB ID: 4LY1), (Hs)HDAC3 (green, PDB ID: 4A69), and (Hs)HDAC8 (orange, PDB ID: 1T69)45,46,47,48. b Coordination of suberoylanilide hydroxamic acid (SAHA; shown as spheres) to (Hs)HDAC841. c Coordination of (Gt)AcuB (M188) within the (Gt)AcuC active center (AlphaFold 3) compared to (Hs)HDAC8 binding with SAHA. d Root Mean Square Fluctuation (RMSF) values (in Å) of Cα atoms obtained from molecular dynamics (MD) simulations in the absence of a ligand (apo; blue) and in the presence of Ap4A (red). e Distance (in Å) between the sulfur (SD) atom of AcuB_M188 and the zinc ion of AcuC in the active site during MD simulations, comparing the apo state (blue) and the Ap4A-bound state (red). f HDX analysis reveals structural differences in the (Gt)AcuC catalytic center when in complex, compared to its individual forms and (Gt)AcuB. g–h Close-up views of the active site in the apo (g) and Ap4A-bound (h) states. The carbon atoms of the AcuB_Zn²⁺-coordinating residues are shown in cyan, while AcuB_M188 and its associated loop are highlighted in yellow. Source data underlying (d, e) are provided as a Source Data file.
