. Author manuscript; available in PMC: 2016 Jan 16.

Published in final edited form as: ACS Chem Biol. 2015 Jan 16;10(1):95–108. doi: 10.1021/cb500846u

Table 1.

Mechanism and kinetic properties of histone lysine acetyltransferase and methyltransferase.

Enzyme			Substrate		Inhibitor/Product
Catalytic mechanism	Group^*	Members^* (species)	K_m (K_d) [μM]	Kinetic Mechanism	K_i [μM]^**	Mechanism^**
Acetyltransferase			Acetyl-coA		coenzyme A
N-ε-lysine activated by deprotonation (by Glu in Gcn5 and MYST); unprotonated lysine directly attacks the carbonyl of acetyl-CoA	Gcn5	Gcn5 (yeast)	2.5 (8.5) (14)	ordered bi-bi, acetyl-coA binds first	6.7 (15)	competitive
		Gcn5 (human)	0.62 (0.56) (14)
		P/CAF (human)	0.98 (0.64) (16), 0.64 (17)		0.57, 0.44 (16)	competitive
	MYST	Esa1 (yeast)	0.9 (18)	ordered bi-bi, acetyl-coA binds first	1.8 (18)	competitive
	p300/CBP	p300 (human)	6.7 (19)	Theorell–Chance mechanism, acetyl-coA binds first	21 (19)	competitive

Methyltransferase			SAM		SAH
Catalytic residue (Tyr in SET9, ? in Dot1) deprotonates histone lysine amino group, which attacks the methyl group of bound SAM	SET containing	SET9 (human)	6.0 (20)	random bi-bi
		SUV39H1 (human)	12 (21)		12 (21)	competitive
		G9a (mouse)	1.8, 2.7 (22)		2.3 (22)	competitive
	non-SET containing	DOT1L (human)	0.67 (23)		0.26 (23)	competitive

Listed enzymes are examples; not all related enzymes shown here

^**

Inhibition mechanisms and Ki values are for small metabolite co-substrate