Horticultural Sciences Department, University of Florida, Gainesville, Florida 32611, United States.
Computing, Environment, and Life Sciences Division, Argonne National Laboratory, Lemont, Illinois 60439, United States.
Biochemistry. 2021 Nov 30;60(47):3555-3565. doi: 10.1021/acs.biochem.1c00613. Epub 2021 Nov 3.
Enzymes have life spans. Analysis of life spans, i.e., lifetime totals of catalytic turnovers, suggests that nonsurvivable collateral chemical damage from the very reactions that enzymes catalyze is a common but underdiagnosed cause of enzyme death. Analysis also implies that many enzymes are moderately deficient in that their active-site regions are not naturally as hardened against such collateral damage as they could be, leaving room for improvement by rational design or directed evolution. Enzyme life span might also be improved by engineering systems that repair otherwise fatal active-site damage, of which a handful are known and more are inferred to exist. Unfortunately, the data needed to design and execute such improvements are lacking: there are too few measurements of life span, and existing information about the extent, nature, and mechanisms of active-site damage and repair during normal enzyme operation is too scarce, anecdotal, and speculative to act on. Fortunately, advances in proteomics, metabolomics, cheminformatics, comparative genomics, and structural biochemistry now empower a systematic, data-driven approach for identifying, predicting, and validating instances of active-site damage and its repair. These capabilities would be practically useful in enzyme redesign and improvement of in-use stability and could change our thinking about which enzymes die young , and why.
酶具有寿命。对寿命的分析，即催化周转的总寿命期，表明酶催化的不可避免的副反应化学损伤是酶死亡的常见但未被诊断出的原因。分析还表明，许多酶都存在中度缺乏，因为它们的活性部位区域并没有自然地免受这种副反应损伤，这为通过合理设计或定向进化来提高酶的活性提供了空间。通过工程系统来修复否则会导致活性部位损伤的致命损伤，也可以延长酶的寿命，目前已知有少数这样的系统，并且推断还存在更多的系统。不幸的是，缺乏设计和执行这些改进所需的数据：寿命的测量数据太少，关于正常酶操作过程中活性部位损伤和修复的程度、性质和机制的现有信息太少，而且过于零散、推测性，无法采取行动。幸运的是，蛋白质组学、代谢组学、化学信息学、比较基因组学和结构生物化学的进步现在使我们能够采用系统的、数据驱动的方法来识别、预测和验证活性部位损伤及其修复的实例。这些功能在酶的重新设计和提高使用稳定性方面具有实际意义，并可能改变我们对哪些酶过早死亡以及为什么会这样的思考。
