水蛭素或水蛭素样因子——这是一个问题：来自天然和合成HLF变体分析的见解

IF 3 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

FEBS Letters Pub Date : 2019-11-16 DOI:10.1002/1873-3468.13683

Christian Müller, Phil Lukas, Michel Böhmert, J. Hildebrandt

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引用次数: 12

摘要

水蛭素样因子1 (HLF1)是一类新的水蛭衍生因子。在以前的研究中，HLF1没有表现出抗凝血活性。在这里，我们描述了HLF1和HLF‐Hyb的自然和合成变体的分析，HLF - Hyb是HLF家族中尚未表征的成员。HLF1的N端修饰对其活性有很大影响。HLF1的一些变体表现出与水蛭素相当的凝血酶抑制活性，而其他变体则降低或没有活性。对HLF‐Hyb变异的分析揭示了中央球状结构域对活动的强烈影响。我们的研究结果表明水蛭素和抑制凝血酶的HLF变异具有相似的作用模式。最后，我们提出并讨论了水蛭素和水蛭素的分类标准。

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Hirudin or hirudin‐like factor ‐ that is the question: insights from the analyses of natural and synthetic HLF variants

The hirudin‐like factor 1 (HLF1) of Hirudo medicinalis belongs to a new class of leech‐derived factors. In previous investigations, HLF1 did not exhibit anticoagulatory activities. Here, we describe the analysis of natural and synthetic variants of HLF1 and HLF‐Hyb, a yet uncharacterized member of the HLF family. Modifications within the N terminus of HLF1 have a strong impact on its activity. Some variants of HLF1 exhibit thrombin‐inhibiting activity comparable to hirudins, whereas others have reduced or no activity. The analyses of HLF‐Hyb variants revealed a strong impact of the central globular domain on activity. Our results indicate a comparable mode of action of hirudins and thrombin‐inhibiting HLF variants. Finally, we propose and discuss criteria for classifying hirudins and HLFs.

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来源期刊

FEBS Letters 生物-生化与分子生物学

CiteScore

6.60

自引率

2.90%

发文量

303

审稿时长

1 months

期刊介绍： FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.