Computational studies on imidazole heme conformations

被引:37
作者
Galstyan, AS
Zariç, SD
Knapp, EW
机构
[1] Free Univ Berlin, Inst Chem, Dept Biol Chem & Pharm, D-14195 Berlin, Germany
[2] Univ Belgrade, Dept Chem, Belgrade 11001, Serbia Monteneg
来源
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY | 2005年 / 10卷 / 04期
关键词
density functional theory calculations; heme-imidazole conformation; propionic acid; reaction field; solvation energy;
D O I
10.1007/s00775-005-0642-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Density functional theory computations of heme with ionized propionic acid groups, axially coordinated with two imidazoles, were performed for different mutual orientations of the imidazole planes. Environmental influences from water or protein were considered with a continuum dielectric medium by solving the Poisson equation. In vacuum, optimized geometries yielded imidazole - heme conformations where the NH groups of imidazoles are oriented toward the heme propionic groups in agreement with data from crystal structures of heme proteins. Conformational free-energy dependencies of the mutual orientation of axially ligated imidazoles calculated in protein ( epsilon = 10) and water (epsilon = 80) environments confirmed the vacuum results, albeit the energy difference between the preferred and the 180 degrees opposite orientations of the imidazole ligand decreased from 3.84 kcal/mol in vacuum to 2.35 and 2.40 kcal/mol in protein and water, respectively. Two main factors determine the imidazole orientation: ( 1) the direct intramolecular electrostatic interactions of propionic groups with the polar NH groups of imidazole and ( 2) the electrostatic interaction of the total dipole moment of the imidazole - heme complex with the reaction field. In vacuum, only the first type of interaction is present, while in a dielectric medium the latter effect becomes competitive at high dielectric constant, resulting in a decrease of the orientational preference. Interestingly, the orientational preference of the imidazole axially ligated to heme becomes even more pronounced, if the negatively charged propionates are neutralized by counter charges that mimic salt bridges or protonation of the propionates.
引用
收藏
页码:343 / 354
页数:12
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