title: The active site architecture in peroxiredoxins: a case study on Mycobacterium tuberculosis AhpE.
abstract: Peroxiredoxins catalyze the reduction of peroxides, a process of vital importance to survive oxidative stress. A nucleophilic cysteine, also known as the peroxidatic cysteine, is responsible for this catalytic process. We used the Mycobacterium tuberculosis alkyl hydroperoxide reductase E (MtAhpE) as a model to investigate the effect of the chemical environment on the specificity of the reaction. Using an integrative structural (R116A - PDB ; F37H - PDB ), kinetic and computational approach, we explain the mutational effects of key residues in its environment. This study shows that the active site residues are specifically oriented to create an environment which selectively favours a reaction with peroxides.
authors.affiliation: Structural Biology Research Center, Oxidative Stress Signaling lab, VIB, Pleinlaan 2, 1050 Brussels, Belgium. joris.messens@vib-vub.be and Brussels Center for Redox Biology, 1050 Brussels, Belgium and Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Brandán
authors.initials: B
authors.lastname: Pedre
authors.affiliation: Brussels Center for Redox Biology, 1050 Brussels, Belgium and Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium and Research Group of General Chemistry, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Laura A H
authors.initials: LA
authors.lastname: van Bergen
authors.affiliation: Structural Biology Research Center, Oxidative Stress Signaling lab, VIB, Pleinlaan 2, 1050 Brussels, Belgium. joris.messens@vib-vub.be and Brussels Center for Redox Biology, 1050 Brussels, Belgium and Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Anna
authors.initials: A
authors.lastname: Palló
authors.affiliation: Structural Biology Research Center, Oxidative Stress Signaling lab, VIB, Pleinlaan 2, 1050 Brussels, Belgium. joris.messens@vib-vub.be and Brussels Center for Redox Biology, 1050 Brussels, Belgium and Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Rosado
authors.affiliation: Structural Biology Research Center, Oxidative Stress Signaling lab, VIB, Pleinlaan 2, 1050 Brussels, Belgium. joris.messens@vib-vub.be and Brussels Center for Redox Biology, 1050 Brussels, Belgium and Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Veronica Tamu
authors.initials: VT
authors.lastname: Dufe
authors.affiliation: Structural Biology Research Center, Oxidative Stress Signaling lab, VIB, Pleinlaan 2, 1050 Brussels, Belgium. joris.messens@vib-vub.be and Brussels Center for Redox Biology, 1050 Brussels, Belgium and Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Inge Van
authors.initials: IV
authors.lastname: Molle
authors.affiliation: Structural Biology Research Center, Oxidative Stress Signaling lab, VIB, Pleinlaan 2, 1050 Brussels, Belgium. joris.messens@vib-vub.be and Brussels Center for Redox Biology, 1050 Brussels, Belgium and Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Khadija
authors.initials: K
authors.lastname: Wahni
authors.affiliation: Structural Biology Research Center, Oxidative Stress Signaling lab, VIB, Pleinlaan 2, 1050 Brussels, Belgium. joris.messens@vib-vub.be and Brussels Center for Redox Biology, 1050 Brussels, Belgium and Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Huriye
authors.initials: H
authors.lastname: Erdogan
authors.affiliation: Research Group of General Chemistry, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Alonso
authors.affiliation: Research Group of General Chemistry, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Frank De
authors.initials: FD
authors.lastname: Proft
authors.affiliation: Structural Biology Research Center, Oxidative Stress Signaling lab, VIB, Pleinlaan 2, 1050 Brussels, Belgium. joris.messens@vib-vub.be and Brussels Center for Redox Biology, 1050 Brussels, Belgium and Structural Biology Brussels, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Joris
authors.initials: J
authors.lastname: Messens
mesh_terms: D020134:Catalytic Domain; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry / Q000378:metabolism; D054464:Peroxiredoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D010545:Peroxides; D054464:Peroxiredoxins