title: Protonation and geometry of histidine rings.
abstract: The presence of H atoms connected to either or both of the two N atoms of the imidazole moiety in a histidine residue affects the geometry of the five-membered ring. Analysis of the imidazole moieties found in histidine residues of atomic resolution protein crystal structures in the Protein Data Bank (PDB), and in small-molecule structures retrieved from the Cambridge Structural Database (CSD), identified characteristic patterns of bond lengths and angles related to the protonation state of the imidazole moiety. Using discriminant analysis, two functions could be defined, corresponding to linear combinations of the four most sensitive stereochemical parameters, two bond lengths (ND1-CE1 and CE1-NE2) and two endocyclic angles (-ND1- and -NE2-), that uniquely identify the protonation states of all imidazole moieties in the CSD and can be used to predict which N atom(s) of the histidine side chains in protein structures are protonated. Updated geometrical restraint target values are proposed for differently protonated histidine side chains for use in macromolecular refinement.
authors.affiliation: Synchrotron Radiation Research Section, MCL, National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: Maura
authors.initials: M
authors.lastname: Malinska
authors.affiliation: Leidos Biomedical Research Inc., Basic Science Program, Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: Miroslawa
authors.initials: M
authors.lastname: Dauter
authors.affiliation: Department of Organic Chemistry, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kowiel
authors.affiliation: Department of Crystallography, Faculty of Chemistry, A. Mickiewicz University, Poznan, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Jaskolski
authors.affiliation: Synchrotron Radiation Research Section, MCL, National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439, USA.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Dauter
mesh_terms: D018360:Crystallography, X-Ray; D030562:Databases, Protein; D006639:Histidine / Q000737:chemistry*; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D011522:Protons; D013237:Stereoisomerism
chemical_list: D007093:Imidazoles; D011506:Proteins; D011522:Protons; D006639:Histidine; C029899:imidazole
keywords: X-ray crystal structure; histidine protonation; hydrogen bond; imidazole; stereochemical restraints