title: Structural and electrostatic asymmetry at the active site in typical and atypical peroxiredoxin dimers.
abstract: The peroxiredoxins (Prx) are ubiquitous peroxidases involved in important biological processes; however, details of their enzymatic mechanism remain elusive. To probe potential dynamics-function relationships, molecular dynamics simulations and electrostatic calculations were performed on the atypical 2-cysteine thiol peroxidase (Tpx) from Streptococcus pneumoniae and results compared to a previous study of a typical 2-cysteine Prx from Trypanosoma cruzi. The analyses indicate a commonality between both typical and atypical Prx: dynamic asymmetry. Asymmetry is observed in structure, fluctuations, and active site electrostatics. Key residues, including Glu150 and Phe153, play roles in the developing asymmetry; furthermore, in the atypical 2-Cys Tpx, Glu150 exhibits conformation fluctuations suggesting involvement in a proton shuttle. The existence of a pathway of connected residues appears to propagate the asymmetry. The commonality of asymmetry and coupling pathways in both typical and atypical Prxs suggests a driving force toward dimer asymmetry as a common feature that plays a functional role in creating one active site with a lower cysteine pK(a).
authors.affiliation: Department of Physics, Wake Forest University, Winston-Salem, North Carolina 27109, USA.
authors.forename: Freddie R
authors.initials: FR
authors.lastname: Salsbury
authors.forename: Ye
authors.initials: Y
authors.lastname: Yuan
authors.forename: Michael H
authors.initials: MH
authors.lastname: Knaggs
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Poole
authors.forename: Jacquelyn S
authors.initials: JS
authors.lastname: Fetrow
mesh_terms: D020134:Catalytic Domain; D019281:Dimerization; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D054464:Peroxiredoxins / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D029702:Schizosaccharomyces pombe Proteins; D055672:Static Electricity; D013296:Streptococcus pneumoniae / Q000201:enzymology
chemical_list: D029702:Schizosaccharomyces pombe Proteins; C515985:Tpx1 protein, S pombe; D054464:Peroxiredoxins