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Thioredoxin and peptide methionine sulfoxide reductase: Convergence of similar structure and function in distinct structural folds
Author(s) -
Gladyshev Vadim N.
Publication year - 2001
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10003
Subject(s) - methionine sulfoxide reductase , thioredoxin , biochemistry , methionine sulfoxide , thioredoxin reductase , active site , peptide , cysteine , biology , amino acid , ferredoxin thioredoxin reductase , structural motif , subfamily , protein structure , peptide sequence , methionine , enzyme , gene
Thioredoxin (Trx) and peptide methionine sulfoxide reductase (PMSR) are small thiol oxidoreductases implicated in antioxidant defense and redox regulation of cellular processes. Here we show that the structures of Trx and PMSR exhibit resemblance in their αβ core regions and that the active site cysteines in two proteins occupy equivalent positions downstream of a central β ‐strand and at the N‐terminus of an α ‐helix. Moreover, we identified a PMSR subfamily that contains an active site CxxC motif (two cysteines separated by two other amino acids) positioned similarly to the catalytic redox active CxxC motif in Trx. However, Trx and PMSR are characterized by distinct ancient folds that differ in both orientation of secondary structures and their patterns. Trx is a member of the Trx‐fold superfamily, whereas PMSR has a unique fold not found in other proteins. The data suggest that similar structures and functions of Trx and PMSR were acquired independently during evolution and point to a general strategy of identifying new redox regulatory proteins. Proteins 2002;46:149–152. © 2001 Wiley‐Liss, Inc.