Histone acetyltransferases: challenges in targeting bi-substrate enzymes

Table 3 Reported catalytic mechanisms for the different HAT families, the enzyme constructs used, and experimental methods applied

Family	Mechanism	Enzyme (amino acids)	Methods	Reference
GNAT	Compulsory-order ternary complex mechanism	KAT2A HAT domain (99–262)	Mutagenesis studies, biochemical studies	[86]
GNAT	Compulsory-order ternary complex mechanism	KAT2B catalytic domain (493–676) and full-length	Kinetic analysis, dead-end substrate mimic inhibitor	[45]
MYST	Ping-pong mechanism	Yeast ESA1 HAT domain (160–435)	Crystal structure, mutagenesis	[91]
	Ping-pong mechanism	KAT8 C-terminal (125–458)	Kinetic analysis, calorimetric binding studies	[88]
	Ternary complex mechanism	Yeast ESA1 full-length and picNuA4 complex	Kinetic analysis, mutagenesis studies	[92]
p300/CBP	Ping-pong mechanism	KAT3B full-length	Kinetic analysis	[93]
	Theorell-Chance mechanism	KAT3B catalytic domain (1284–1673)	Chemical probe	[94]
	Theorell-Chance mechanism	KAT3B semi-synthetic heterodimeric HAT domain (1287–1652)	Crystal structure, bi-substrate inhibitor, mutagenesis, kinetic analysis	[95]