Department of Environmental Medicine, Nippon Medical School, Tokyo, Japan.
Amino Acids. 2011 Jun;41(1):59-72. doi: 10.1007/s00726-010-0508-4. Epub 2010 Feb 24.
Recently, redox-regulated biological reactions have been elucidated. In the regulation of these reactions, redox-sensing molecular switches function as unique biological machineries that modulate the functional proteins present in enzymes, transcriptional factors, sensor proteins, and transcriptional factor modulators. The redox-sensing cysteine residues and the disulfide bond formed between these cysteine residues serve as redox-sensing molecular switches; these switches sense cellular oxidizing factors such as oxygen, reactive oxygen species, and cellular reducing factors such as thioredoxin (Trx), glutathione (GSH), and their family molecules. Depending on the redox status, the switch directly modulates the protein function via the "locking and unlocking" of the critically functional residue or indirectly modulates the protein function via "protein conformational changes," which affects the functioning of a distantly located critical residue in an allostery-like fashion or a topology change. Redox-sensing switches can be classified into two types-intramolecular (intrasubunit) and intermolecular (intersubunit) ones. Further, depending on the sensing specificity to reducing factors, the switch subtype is classified into Trx, GSH, or their family molecules-specific type. This review focused on the intermolecular redox-sensing switches found in various proteins.
近年来，氧化还原调控的生物反应已经被阐明。在这些反应的调控中，氧化还原感应分子开关作为独特的生物机制，调节存在于酶、转录因子、传感器蛋白和转录因子调节剂中的功能蛋白。氧化还原感应半胱氨酸残基和这些半胱氨酸残基之间形成的二硫键作为氧化还原感应分子开关；这些开关感应细胞氧化因子，如氧、活性氧物种，以及细胞还原因子，如硫氧还蛋白 (Trx)、谷胱甘肽 (GSH) 及其家族分子。根据氧化还原状态，开关通过关键功能残基的“锁定和解锁”直接调节蛋白质功能，或者通过“蛋白质构象变化”间接调节蛋白质功能，以类似变构的方式影响远处关键残基的功能或拓扑变化。氧化还原感应开关可以分为两种类型-分子内（亚基内）和分子间（亚基间）。此外，根据对还原因子的感应特异性，开关亚型分为 Trx、GSH 或其家族分子特异性类型。这篇综述重点介绍了各种蛋白质中发现的分子间氧化还原感应开关。
