title: Revisiting sulfur H-bonds in proteins: The example of peroxiredoxin AhpE.
abstract: In many established methods, identification of hydrogen bonds (H-bonds) is primarily based on pairwise comparison of distances between atoms. These methods often give rise to systematic errors when sulfur is involved. A more accurate method is the non-covalent interaction index, which determines the strength of the H-bonds based on the associated electron density and its gradient. We applied the NCI index on the active site of a single-cysteine peroxiredoxin. We found a different sulfur hydrogen-bonding network to that typically found by established methods, and we propose a more accurate equation for determining sulfur H-bonds based on geometrical criteria. This new algorithm will be implemented in the next release of the widely-used CHARMM program (version 41b), and will be particularly useful for analyzing water molecule-mediated H-bonds involving different atom types. Furthermore, based on the identification of the weakest sulfur-water H-bond, the location of hydrogen peroxide for the nucleophilic attack by the cysteine sulfur can be predicted. In general, current methods to determine H-bonds will need to be reevaluated, thereby leading to better understanding of the catalytic mechanisms in which sulfur chemistry is involved.
authors.affiliation: Research Group of General Chemistry, Vrije Universiteit Brussel, 1050 Brussels, Belgium.|Structural Biology Research Center, VIB, 1050 Brussels, Belgium.|Brussels Center for Redox Biology, 1050 Brussels, Belgium.|Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Laura A H
authors.initials: LA
authors.lastname: van Bergen
authors.affiliation: Research Group of General Chemistry, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Alonso
authors.affiliation: Structural Biology Research Center, VIB, 1050 Brussels, Belgium.|Brussels Center for Redox Biology, 1050 Brussels, Belgium.|Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Anna
authors.initials: A
authors.lastname: Palló
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, SE-14183 Huddinge, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Nilsson
authors.affiliation: Research Group of General Chemistry, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: De Proft
authors.affiliation: Structural Biology Research Center, VIB, 1050 Brussels, Belgium.|Brussels Center for Redox Biology, 1050 Brussels, Belgium.|Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Joris
authors.initials: J
authors.lastname: Messens
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry; D002384:Catalysis; D020134:Catalytic Domain; D003545:Cysteine / Q000737:chemistry; D006838:Hydrocarbons / Q000737:chemistry; D006860:Hydrogen Bonding; D006861:Hydrogen Peroxide / Q000737:chemistry; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009169:Mycobacterium tuberculosis / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D054464:Peroxiredoxins / Q000737:chemistry*; D012984:Software; D013438:Sulfhydryl Compounds; D013455:Sulfur / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D006838:Hydrocarbons; D013438:Sulfhydryl Compounds; D014867:Water; D013455:Sulfur; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D003545:Cysteine; D010100:Oxygen