Figure 7.

Histidine interaction type correlates with histidine-predicted pK_a. (A) Distribution of pK_a values of histidine in high-resolution X-ray structures calculated using PypKA (see the Methods section). The pK_a values correspond to 36,393 His residues which are not interacting with metals. The pK_a peak value of the distribution is 6.3. The His pK_a values are categorized into three groups: low pK_a His with pK_a < 5.3 (10,231 His instances), high pK_a category with pK_a > 7.3 (4530 instances), and medium pK_a His with 5.3 ≤ pK_a ≤ 7.3 (21,632 instances). For each of the His in the three pK_a groups, all pairwise interactions between His and Phe, Tyr, or Trp were geometrically analyzed and classified as H-bonds, π-stacked, or CH–π. For each group of pK_a values of His, the occurrence of interactions is normalized independently for each pairwise interaction. (B–D) Fractions of pairwise interactions of His, depending on its predicted pK_a value, interacting with aromatic residues via (B) π-stacked, (C) CH-π geometries, or (D) H-bonds of Tyr.