Suntsova Tatiana P, Beda Nataliya V, Nedospasov Andrei A
Institute of Molecular Genetics, Russian Academy of Sciences, 2 Kurchatov Sq., Moscow, 123182, Russia.
IUBMB Life. 2002 Nov;54(5):281-92. doi: 10.1080/15216540215677.
It is known that potentially reactive groups of the protein molecule may be most efficiently nitros(yl)ated only when located within hydrophobic globules or built into the membrane. N1-nitrosotryptophan (NOW) is a stable product of nitrosation in vitro. However, the NOW fraction in proteins is small in ordinary proteins. It suggests the existence of unknown mechanisms preventing the accumulation of NOW. Here we show that these mechanisms are underlain by the protein structure. Analysis of protein structure databases to explore the atomic surroundings of tryptophan residues revealed preferential selection of certain surroundings. N(E) atoms of tryptophan residues, which are the targets for nitrosation, have usually polar and nucleophilic groups in their environment. Residues of Asp, Glu, Cys, His, and Met act as catalysts of denitrosation (internal denitrosilase). We found that short peptides with the same residues possessed denitrosilase activity even in solution. This selection might explain both the resistance of tryptophan residues in proteins to nitrosation and the mechanisms of chemical communication by means of reversible nitrosation of proteins.
已知蛋白质分子中潜在的反应性基团只有位于疏水球体内或嵌入膜中时，才可能最有效地被亚硝基（化）。N1-亚硝基色氨酸（NOW）是体外亚硝化的稳定产物。然而，普通蛋白质中NOW在蛋白质中的比例很小。这表明存在未知机制阻止NOW的积累。在这里我们表明，这些机制是由蛋白质结构决定的。对蛋白质结构数据库进行分析以探索色氨酸残基的原子环境，发现了对某些环境的优先选择。色氨酸残基的N（E）原子是亚硝化的靶点，其周围环境通常具有极性和亲核基团。天冬氨酸、谷氨酸、半胱氨酸、组氨酸和蛋氨酸的残基充当去亚硝基化的催化剂（内源性去亚硝基化酶）。我们发现具有相同残基的短肽即使在溶液中也具有去亚硝基化酶活性。这种选择可能既解释了蛋白质中色氨酸残基对亚硝化的抗性，也解释了通过蛋白质可逆亚硝化进行化学通讯的机制。
