Thioredoxin-related protein of 14 kDa is an efficient L-cystine reductase and S-denitrosylase

Irina Pader; Rajib Sengupta; Marcus CebulaJianqiang XuJon O. LundbergArne HolmgrenKatarina JohanssonElias S. J. Arnér

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Thioredoxin-related protein of 14 kDa is an efficient L-cystine reductase and S-denitrosylase

机译：Thioredoxin-related protein of 14 kDa is an efficient L-cystine reductase and S-denitrosylase

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Thioredoxin-related protein of 14 kDa (TRP14, also called TXNDC17 for thioredoxin domain containing 17, or TXNL5 for thioredoxinlike 5) is an evolutionarily well-conserved member of the thioredoxin (Trx)-fold protein family that lacks activity with classical Trx1 substrates. However, we discovered here that human TRP14 has a high enzymatic activity in reduction of L-cystine, where the catalytic efficiency (2,217 min~(-1)·μM~(-1)) coupled to Trx reductase 1 (TrxR1) using NADPH was fivefold higher compared with Trx1 (418 min~(-1)·μM~(-1)). Moreover, the L-cystine reduction with TRP14 was in contrast to that of Trx1 fully maintained in the presence of a protein disulfide substrate of Trx1 such as insulin, suggesting that TRP14 is a more dedicated L-cystine reductase compared with Trx1. We also found that TRP14 is an efficient S-denitrosylase with similar efficiency as Trx1 in catalyzing TrxR1-dependent denitrosylation of S-nitrosylated glutathione or of HEK293 cell-derived S-nitrosoproteins. Consequently, nitrosylated and thereby inactivated caspase 3 or cathepsin B could be reactivated through either Trx1- or TRP14-catalyzed denitrosylation reactions. TRP14 was also, in contrast to Trx1, completely resistant to inactivation by high concentrations of hydrogen peroxide. The oxidoreductase activities of TRP14 thereby complement those of Trx1 and must therefore be considered for the full understanding of enzymatic control of cellular thiols and nitrosothiols.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第19期|6964-6969|共6页
作者
Irina Pader; Rajib Sengupta; Marcus CebulaJianqiang XuJon O. LundbergArne HolmgrenKatarina JohanssonElias S. J. Arnér;
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作者单位

Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet;

Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
protein; reductase; denitrosylase;

Thioredoxin-related protein of 14 kDa is an efficient L-cystine reductase and S-denitrosylase

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