Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
FEBS J. 2020 Oct;287(19):4300-4309. doi: 10.1111/febs.15545. Epub 2020 Sep 17.
Pseudoenzymes are proteins that are evolutionarily related to active enzymes, but lack relevant catalytic activity. As obligate intracellular pathogens, viruses complete their life cycle fully dependent on the cellular supplies of macromolecule and energy. Traditionally, studies of viral proteins sharing high homology with host counterparts reveal insightful mechanisms by which host signaling pathways are delicately regulated. Recent investigations into the action of cellular pseudoenzymes elucidate diverse molecular means how enzymes are differentially controlled under various physiological conditions, hinting to the potential that pathogens may exploit these regulatory modalities. To date, there have been three types of viral pseudoenzymes reported and our understanding concerning their mechanism of regulation is rudimentary at best. However, it is clear that viral pseudoenzymes are emerging with surprising functions in infection and immunity, and we are only at the beginning to understand this new group of enzyme regulators. In this review, we will summarize current knowledge in viral pseudoenzymes and provide a perspective for future research.
拟酶是在进化上与活性酶相关但缺乏相关催化活性的蛋白质。作为专性细胞内病原体,病毒完全依赖于细胞大分子和能量的供应来完成其生命周期。传统上,对与宿主具有高度同源性的病毒蛋白的研究揭示了宿主信号通路如何被精细调控的深入机制。最近对细胞拟酶作用的研究阐明了在各种生理条件下酶如何被差异化控制的多种分子手段,提示病原体可能利用这些调节方式。迄今为止,已经报道了三种类型的病毒拟酶,我们对其调节机制的理解充其量还处于初级阶段。然而,很明显,病毒拟酶在感染和免疫中具有令人惊讶的功能,我们才刚刚开始理解这一新的酶调节剂群体。在这篇综述中,我们将总结病毒拟酶的现有知识,并为未来的研究提供一个视角。