TABLE 1.

Characteristics of ionizable side chains in proteins

This is a summary of 541 pK values tabulated from the literature (5). The values were reported under various conditions for 78 folded proteins.

Group	Contenta	Buriedb	pK value in alanine pentapeptides (pKint)c	Average pK value	Low pK value	High pK value	No. of measurements
	%	%
Asp	5.2	56	3.9	3.5 ± 1.2	0.5	9.2	139
Glu	6.5	48	4.3	4.2 ± 0.9	2.1	8.8	153
His	2.2	72	6.5	6.6 ± 1.0	2.4	9.2	131
Cys	1.2	90	8.6	6.8 ± 2.7	2.5	11.1	25
Tyr	3.2	67	9.8	10.3 ± 1.2	6.1	12.1	20
Lys	5.9	34	10.4	10.5 ± 1.1	5.7	12.1	35
Arg	5.1	56	12.3d
C terminus			3.7	3.3 ± 0.8	2.4	5.9	22
N terminus			8.0	7.7 ± 0.5	6.8	9.1	16

^aThis is the current average % amino acid content of proteins from all three domains of life: Bacteria, Archaea, and Eukaryota (12). For comparison, the most abundant amino acid is Leu (10.3%), and the least abundant is Trp (1.1%).

^bThe % buried is based on an analysis of 61 proteins by Lesser and Rose (13). The % buried is for just the ionizable group: the carboxyl groups of Asp and Glu, the imidazole of His, the –SH of Cys, the –OH of Tyr, the amino group of Lys, and the guanidinium of Arg.

^cpK values are from Ref. 11, and the value for Asp was corrected in Ref. 5.

^dA value of 12.48 is given for Arg in Ref. 49. A correction for the negative charge on the carboxyl group present in Arg gives a pK of ≈ 12.3.