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Analysis of the peroxiredoxin family: Using active-site structure and sequence information for global classification and residue analysis

Fetrow, Jacquelyn S.

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abstract
Peroxiredoxins (Prxs) are a widespread and highly expressed family of cysteine-based peroxidases that react very rapidly with H2O2, organic peroxides, and peroxynitrite. Correct subfamily classification has been problematic because Prx subfamilies are frequently not correlated with phylogenetic distribution and diverge in their preferred reductant, oligomerization state, and tendency toward overoxidation. We have developed a method that uses the Deacon Active Site Profiler (DASP) tool to extract functional-site profiles from structurally characterized proteins to computationally define subfamilies and to identify new Prx subfamily members from GenBank(nr). For the 58 literature-defined Prx test proteins, 57 were correctly assigned, and none were assigned to the incorrect subfamily. The >3500 putative Prx sequences identified were then used to analyze residue conservation in the active site of each Prx subfamily. Our results indicate that the existence and location of the resolving cysteine vary in some subfamilies (e.g., Prx5) to a greater degree than previously appreciated and that interactions at the A interface (common to Prx5, Tpx, and higher order AhpC/Prx1 structures) are important for stabilization of the correct active-site geometry. Interestingly, this method also allows us to further divide the AhpC/Prx1 into four groups that are correlated with functional characteristics. The DASP method provides more accurate subfamily classification than PSI-BLAST for members of the Prx family and can now readily be applied to other large protein families.
description
This is a preprint version; the version of record is available at http://dx.doi.org/10.1002/prot.22396.
subject
functional-site profile
mechanistic determinants
function annotation
misannotation
thiol peroxidase
thioredoxin peroxidase
AhpC
Prx
BCP
Tpx
citation
3 (issue)
79 (volume)
contributor
Nelson, Kimberly J. (author)
Knutson, Stacy T. (author)
Soito, Laura (author)
Klomsiri, Chananat (author)
Poole, Leslie B. (author)
Fetrow, Jacquelyn S. (author)
date
2014-01-10T20:13:49Z (accessioned)
2014-01-10T20:13:49Z (available)
2011 (issued)
identifier
Nelson, K.J.; Knutson, S.T.; Soito, L.; Klomsiri, C.; Poole, L.B.; Fetrow, J.S. (2011). "Analysis of the peroxiredoxin family: Using active-site structure and sequence information for global classification and residue analysis." Proteins, 79(3):947-64. Available at http://dx.doi.org/10.1002/prot.22936. (citation)
http://hdl.handle.net/10339/39102 (uri)
http://dx.doi.org/10.1002/prot.22936 (uri)
publisher
Wiley
source
Proteins: Structure, Function, and Bioinformatics
title
Analysis of the peroxiredoxin family: Using active-site structure and sequence information for global classification and residue analysis
type
Article

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