Methionine residues may protect proteins from critical oxidative damage
Methionine residues may protect proteins from critical oxidative damage
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DOI：
10.1016/s0047-6374(98)00152-3
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发表时间：
1999-03-15
影响因子：
5.3
通讯作者：
Stadtman, ER
中科院分区：
文献类型：
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作者：
Levine, RL;Berlett, BS;Stadtman, ER
半胱氨酸和蛋氨酸是蛋白质中常见的两种含硫残基。半胱氨酸残基在许多酶的催化循环中起作用，它们形成二硫键，有助于蛋白质结构。相反，蛋氨酸残基的关键功能尚不清楚。我们建议，蛋氨酸残基构成一个重要的抗氧化防御机制。多种氧化剂容易与甲硫氨酸反应形成甲硫氨酸亚砜，并且表面暴露的甲硫氨酸残基产生极高浓度的反应物，从而提供氧化剂的有效清除。以大肠杆菌为模型，研究了过氧化氢暴露对谷氨酰胺合成酶的影响。16个甲硫氨酸残基中有8个可被氧化，对活性影响不大。发现可氧化的甲硫氨酸残基相对暴露于表面，而完整的残基通常埋在蛋白质的核心内。此外，易感残基物理上排列成阵列，其保护活性位点的入口。甲硫氨酸亚砜可通过甲硫氨酸亚砜还原酶还原回甲硫氨酸，从而催化放大每个甲硫氨酸残基的抗氧化潜力。鉴于氧化应激在衰老过程中的重要性，蛋氨酸残基在衰老过程中作为抗氧化剂的潜在功能应进行实验研究。出版社：Elsevier Science爱尔兰有限公司
Cysteine and methionine are the two sulfur-containing residues normally found in proteins. Cysteine residues function in the catalytic cycle of many enzymes, and they form disulfide bonds which contribute to protein structure. In contrast: the key functions of methionine residues are not known. We propose that methionine residues constitute an important antioxidant defense mechanism. A variety of oxidants react readily with methionine to form methionine sulfoxide, and surface exposed methionine residues create an extremely high concentration of reactant, providing for efficient scavenging of oxidants. The effect of hydrogen peroxide exposure upon glutamine synthetase from Escherichia coli was studied as an in vitro model system. Eight of the sixteen methionine residues could be oxidized with little effect on activity. The oxidizable methionine residues were found to be relatively surface exposed while the intact residues were generally buried within the core of the protein. Further, the susceptible residues were physically arranged in an array which guarded the entrance to the active site. Methionine sulfoxide can be reduced back to methionine by the enzyme methionine sulfoxide reductase, providing a catalytic amplification of the antioxidant potential of each methionine residue. Given the importance of oxidative stress during aging, the potential function of methionine residues as antioxidants during aging should be investigated experimentally. Published by Elsevier Science Ireland Ltd.