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Hydrogen bonding is the prime determinant of carboxyl p K a values at the N‐termini of α‐helices
Author(s) -
Porter Melissa A.,
Hall Jordan R.,
Locke James C.,
Jensen Jan H.,
Molina Pablo A.
Publication year - 2006
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.20879
Subject(s) - chemistry , hydrogen bond , crystallography , helix (gastropod) , stereochemistry , molecule , biology , ecology , organic chemistry , snail
Experimentally determined mean p K a values of carboxyl residues located at the N‐termini of α‐helices are lower than their overall mean values. Here, we perform three types of analyses to account for this phenomenon. We estimate the magnitude of the helix macrodipole to determine its potential role in lowering carboxyl p K a values at the N‐termini. No correlation between the magnitude of the macrodipole and the p K a values is observed. Using the p K a program propKa we compare the molecular surroundings of 18 N‐termini carboxyl residues versus 233 protein carboxyl groups from a previously studied database. Although p K a lowering interactions at the N‐termini are similar in nature to those encountered in other protein regions, p K a lowering backbone and side‐chain hydrogen bonds appear in greater number at the N‐termini. For both Asp and Glu, there are about 0.5 more hydrogen bonds per residue at the N‐termini than in other protein regions, which can be used to explain their lower than average p K a values. Using a QM‐based p K a prediction model, we investigate the chemical environment of the two lowest Asp and the two lowest Glu p K a values at the N‐termini so as to quantify the effect of various p K a determinants. We show that local interactions suffice to account for the acidity of carboxyl residues at the N‐termini. The effect of the helix dipole on carboxyl p K a values, if any, is marginal. Backbone amide hydrogen bonds constitute the single biggest contributor to the lowest carboxyl p K a values at the N‐termini. Their estimated p K a lowering effects range from about 1.0 to 1.9 p K a units. Proteins 2006. © 2006 Wiley‐Liss, Inc.