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Variability in the pKa of histidine side‐chains correlates with burial within proteins
Author(s) -
Edgcomb Stephen P.,
Murphy Kenneth P.
Publication year - 2002
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10177
Subject(s) - histidine , polar , chemistry , acid dissociation constant , side chain , stereochemistry , chemical physics , crystallography , computational chemistry , amino acid , biochemistry , aqueous solution , organic chemistry , physics , polymer , astronomy
Acidic pKas of histidines buried within the protein interior are frequently rationalized on the contradictory basis of either polar interactions within the protein or the effects of a hydrophobic environment. To examine these relationships, we surveyed the buried surface area, depth of burial, polar interactions, and crystallographic temperature factors of histidines of known pKa. It has been found that buried environments of histidines do not always result in acidic pKas. Instead, the variability of histidine pKas increases for residues where the majority of the side‐chain is buried. Because buried histidines are always found in mixed polar/apolar environments, multiple environmental contributions to pKa values must be considered. However, the quantitative relationships between heterogeneous environments and pKa values are not immediately apparent from the available data. Proteins 2002;49:1–6. © 2002 Wiley‐Liss, Inc.