缺氧诱导因子羟化酶的生物化学特性

IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Giorgia Fiorini, Christopher J. Schofield
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引用次数: 0

摘要

缺氧诱导因子是一种α、β二聚体转录因子,在人类和其他动物体内介导对缺氧的慢性反应。属于铁(II)和 2-氧代戊二酸(2OG)依赖性加氧酶超家族两个不同结构亚家族的蛋白羟化酶可修饰 HIFα。由 PHD 催化的 HIFα 原醛羟化可调节 HIFα 水平,进而调节 α、β-HIF 水平。由抑制 HIF 的因子(FIH)催化的 HIFα 天冬酰胺羟化可调节 α、β-HIF 的转录活性。PHDs 和 FIH 的活性受氧气供应量的调节,使它们能够充当缺氧传感器。我们概述了 HIF 羟化酶的生物化学,讨论了它们的动力学和结构特性可能会根据它们在 HIF 系统中的作用进行调整的证据。我们还讨论了未来研究和治疗调节的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Biochemistry of the hypoxia-inducible factor hydroxylases

Biochemistry of the hypoxia-inducible factor hydroxylases

The hypoxia-inducible factors are α,β-heterodimeric transcription factors that mediate the chronic response to hypoxia in humans and other animals. Protein hydroxylases belonging to two different structural subfamilies of the Fe(II) and 2-oxoglutarate (2OG)-dependent oxygenase superfamily modify HIFα. HIFα prolyl-hydroxylation, as catalysed by the PHDs, regulates HIFα levels and, consequently, α,β-HIF levels. HIFα asparaginyl-hydroxylation, as catalysed by factor inhibiting HIF (FIH), regulates the transcriptional activity of α,β-HIF. The activities of the PHDs and FIH are regulated by O2 availability, enabling them to act as hypoxia sensors. We provide an overview of the biochemistry of the HIF hydroxylases, discussing evidence that their kinetic and structural properties may be tuned to their roles in the HIF system. Avenues for future research and therapeutic modulation are discussed.

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来源期刊
Current Opinion in Chemical Biology
Current Opinion in Chemical Biology 生物-生化与分子生物学
CiteScore
13.30
自引率
1.30%
发文量
113
审稿时长
74 days
期刊介绍: COCHBI (Current Opinion in Chemical Biology) is a systematic review journal designed to offer specialists a unique and educational platform. Its goal is to help professionals stay informed about the growing volume of information in the field of Chemical Biology through systematic reviews.
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