Chemistry Research Laboratory and The Oxford Centre for Integrative Systems Biology, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
Trends Biochem Sci. 2011 Jan;36(1):7-18. doi: 10.1016/j.tibs.2010.07.002. Epub 2010 Aug 20.
Pioneering work in the 1960s defined prolyl and lysyl hydroxylations as physiologically important oxygenase-catalyzed modifications in collagen biosynthesis; subsequent studies demonstrated that extracellular epidermal growth factor-like domains were hydroxylated at aspartyl and asparaginyl residues. More recent work on the hypoxia-sensing mechanism in animals has shown that prolyl and asparaginyl hydroxylation of the hypoxia-inducible transcription factor play central roles in sensing hypoxia, by regulating protein-protein interactions in an oxygen-dependent manner. The collective results imply that protein hydroxylation is more common than previously perceived. Most protein hydroxylases employ Fe(II) as a cofactor, and 2-oxoglutarate and oxygen as co-substrates. Related enzymes catalyze the demethylation of N(ɛ)-methyl lysine residues in histones and of N-methylated nucleic acids, as well as hydroxylation of 5-methyl cytosine in DNA and 5-methoxycarbonylmethyluridine at the wobble position of tRNA. The combination of new molecular biological and analytical techniques is likely to reveal further roles for oxygenase-mediated modifications to biomacromolecules.
20 世纪 60 年代的开创性工作将脯氨酰和赖氨酰羟化定义为胶原蛋白生物合成中生理上重要的加氧酶催化修饰；随后的研究表明，细胞外表皮生长因子样结构域在天冬氨酸和天冬酰胺残基上发生羟化。最近关于动物缺氧感应机制的研究表明，缺氧诱导转录因子的脯氨酰和天冬酰胺羟化在缺氧感应中起着核心作用，通过以氧依赖的方式调节蛋白质-蛋白质相互作用。综合结果表明，蛋白质羟化比以前认为的更为普遍。大多数蛋白质羟化酶以 Fe(II)作为辅助因子，并以 2-氧戊二酸和氧气作为共底物。相关酶催化组蛋白中 N(ɛ)-甲基赖氨酸残基和 N-甲基化核酸的去甲基化，以及 DNA 中 5-甲基胞嘧啶和 tRNA 摆动位置上的 5-甲氧基羰基甲基尿嘧啶的羟化。新的分子生物学和分析技术的结合可能会揭示氧合酶介导的生物大分子修饰的进一步作用。
