Premium
Trans ‐substitution of the proximal hydrogen bond in myoglobin: II. Energetics, functional consequences, and implications for hemoglobin allostery
Author(s) -
Barrick Doug
Publication year - 2000
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/(sici)1097-0134(20000601)39:4<291::aid-prot30>3.0.co;2-a
Subject(s) - myoglobin , chemistry , hydrogen bond , ligand (biochemistry) , crystallography , stereochemistry , histidine , molecule , enzyme , biochemistry , receptor , organic chemistry
The trans‐substituted histidine to glycine mutant of sperm whale myoglobin (H93G Mb) is used to study energetics of proximal hydrogen bonding, proximal ligand‐heme interactions, and coupling to distal ligand binding. Comparison of mono‐ and dimethylimidazole structural isomers shows that the hydrogen bond between the proximal ligand and the neighboring Ser92 hydroxyl (position F7) is stabilizing. The range of hydrogen bond stabilities measured here for different distal ligand complexes ranges from ‐0.7 kcal/mol (monomethylimidazole isomers to MbCO) to ‐4.1 kcal/mol (dimethylimidazole isomers to MbCN). This range of hydrogen bond stabilities, which is similar to that seen in protein mutagenesis unfolding studies, demonstrates the high sensitivity of the hydrogen bond to modest structural perturbations. The degree to which the 2‐methyl group destabilizes proximal ligand binding is found to depend inversely on the total electronic spin. For monomethylimidazole proximal ligands, distal ligand binding weakens the proximal hydrogen bond compared to deoxyMb. Surprisingly, this trend is largely reversed for the dimethylimidazole proximal ligands. These results demonstrate strong coupling between the proximal protein matrix and distal ligand binding. These results provide an explanation for the strong avoidance of hydrogen bonding residues at position F7 in hemoglobin sequences. Proteins 2000;39:291–308. © 2000 Wiley‐Liss, Inc.