Details

Autor(en) / Beteiligte

• Zarić, Snežana D
• Popović, Dragan M
• Knapp, Ernst-Walter

Titel

Factors Determining the Orientation of Axially Coordinated Imidazoles in Heme Proteins

Ist Teil von

• Biochemistry (Easton), 2001-07, Vol.40 (26), p.7914-7928

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• Factors determining conformations of imidazole axially coordinated to heme in heme proteins were investigated by analyzing 693 hemes in 432 different crystal structures of heme proteins from the Protein Data Bank (PDB), where at least one histidine is ligated to heme. The results from a search of the PDB for protein structures were interpreted with molecular force field computations. Analysis of data from these crystal structures indicated that there are two main factors that determine the orientations of imidazole ligated to heme. These are the interactions of imidazole with the propionic acid side chains of heme and with the histidine backbone. From the analysis of the crystal structures of heme proteins, it turned out that the hydrogen bonding pattern is often not decisive, though it is probably used by nature to fine-tune the orientation of imidazole axially ligated to heme. We found that in many heme proteins the NδH group of imidazole ligated to heme can assume a number of different hydrogen bonds and that in mutant structures the orientation of the ligated imidazole often does not change significantly, although the mutant altered the hydrogen bonding scheme involving the imidazole. Data from crystal structures of heme proteins show that there are preferred orientations of imidazoles with respect to heme. Generally, the NδH group of imidazole is oriented toward the propionic acid groups of the heme. In some cases, the NδH group of imidazole is close to only one of the propionic acid groups, but it is practically never oriented in the opposite direction. The imidazole also adopts a preferred orientation with respect to its histidine backbone such that the plane of the imidazole ring is practically never parallel to the Cα−Cβ bond of its histidine backbone. For a given conformation of histidine backbone with respect to heme, as well as imidazole with respect to histidine backbone, the orientation of the imidazole with respect to heme is uniquely determined, since the three orientations depend on each other. Hence, the interaction of the imidazole with the backbone also influences the orientation of the imidazole with respect to the heme. Force field computations are in agreement with experimental data. With this method, we showed that there is an energy minimum when the NδH group of the imidazole is oriented toward the propionic acid groups and that there are minima of energy for orientations where the imidazole ring is orthogonal to the plane defined by the Cα−Cβ and Cβ−Cγ bonds of the histidine. The computations also demonstrated that these interactions are mainly of electrostatic origin. By taking into account these two major factors, we were able to understand the orientations of axially coordinated imidazoles for all groups of heme proteins, except for the group of cytochrome c peroxidase. In this group, the orientation of the imidazole is determined by a strong hydrogen bond of the NδH group with Asp235.