Probing altered enzyme activity in the biochemical characterization of cancer.
Probing altered enzyme activity in the biochemical characterization of cancer.
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DOI：
10.1042/bsr20212002
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发表时间：
2022-02-25
影响因子：
4
通讯作者：
Sohl CD
中科院分区：
文献类型：
--
作者：
Adam MAA;Sohl CD
酶已经进化到以必要的速度、位置和时间催化它们的精确反应，以促进我们的发展，回应各种侮辱和挑战，并保持健康、平衡的状态。酶通过其独特的动力学参数，无数的调节策略，以及对环境的敏感性，包括底物浓度和pH，实现了这一非凡的壮举。癌症基因组图谱(TCGA)强调了酶的微调活性可能以多种方式被破坏，导致癌症的发展和进展，通常是由于体细胞和/或遗传基因改变。Kcat、Km和kcat/Km等动力学常数不局限于酶学家的领域，而是信息丰富的参数，可以以有形的方式影响癌症患者--这些参数可用于对肿瘤驱动因素突变和乘客突变进行分类，建立癌细胞驱动患者肿瘤的途径，评估抗癌药物的选择性和有效性，确定治疗耐药机制，等等。在这篇综述中，我们将讨论酶活性的变化，主要是通过体细胞突变，如何导致动力学参数的改变，新的活性，或构象和寡聚的变化。我们还将讨论肿瘤微环境的变化如何影响酶的活性，并简要描述酶学如何与其他强大的工具相结合，并为我们提供对癌症的化学和分子机制的巨大洞察。
Enzymes have evolved to catalyze their precise reactions at the necessary rates, locations, and time to facilitate our development, to respond to a variety of insults and challenges, and to maintain a healthy, balanced state. Enzymes achieve this extraordinary feat through their unique kinetic parameters, myriad regulatory strategies, and their sensitivity to their surroundings, including substrate concentration and pH. The Cancer Genome Atlas (TCGA) highlights the extraordinary number of ways in which the finely tuned activities of enzymes can be disrupted, contributing to cancer development and progression often due to somatic and/or inherited genetic alterations. Rather than being limited to the domain of enzymologists, kinetic constants such as kcat, Km, and kcat/Km are highly informative parameters that can impact a cancer patient in tangible ways—these parameters can be used to sort tumor driver mutations from passenger mutations, to establish the pathways that cancer cells rely on to drive patients’ tumors, to evaluate the selectivity and efficacy of anti-cancer drugs, to identify mechanisms of resistance to treatment, and more. In this review, we will discuss how changes in enzyme activity, primarily through somatic mutation, can lead to altered kinetic parameters, new activities, or changes in conformation and oligomerization. We will also address how changes in the tumor microenvironment can affect enzymatic activity, and briefly describe how enzymology, when combined with additional powerful tools, and can provide us with tremendous insight into the chemical and molecular mechanisms of cancer.
影响因子：
4.1
作者：
Kim J;Song I;Jo A;Shin JH;Cho H;Eoff RL;Guengerich FP;Choi JY
通讯作者：
Choi JY