Saturated fatty acid- and/or monounsaturated fatty acid-containing-phosphatidic acids selectively interact with and activate phosphoglycerate mutase 1

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports Pub Date : 2025-09-29 DOI:10.1016/j.bbrep.2025.102285

Kamila Dilimulati , Naoto Yachida , Fumi Hoshino, Fumio Sakane

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引用次数: 0

Abstract

This study aimed to identify the target proteins of 16:0/16:0-phosphatidic acid (PA), which is produced by diacylglycerol kinases (DGKs) α, δ, and ζ. We identified phosphoglycerate mutase 1 (PGAM1), a key glycolytic enzyme that catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate, as a PA-binding protein with a stronger affinity for PA than for other phospholipids, including phosphatidylinositol, phosphatidylinositol 4-monophosphate, phosphatidylinositol 4,5-bisphosphate, cardiolipin, phosphatidylserine, phosphatidylglycerol, phosphatidylcholine, and sphingomyelin. PGAM1 preferentially binds to saturated fatty acid (SFA)- and/or monounsaturated fatty acid (MUFA)-containing PAs, such as 16:0/16:0-, 16:0/18:1-, 18:0/18:0-, 18:0/18:1-, and 18:1/18:1-PA, compared to polyunsaturated fatty acid-containing PAs, such as 18:0/20:4- and 18:0/22:6-PA. Notably, 16:0/16:0- and 16:0/18:1-PA altered the secondary conformation of PGAM1 and substantially enhanced its activity. Interestingly, PGAM1 interacted with DGKδ and ζ, but not with DGKα. These findings indicate that SFA- and/or MUFA-containing-PAs selectively interact with PGAM1, a promising therapeutic target for cancer, type 2 diabetes mellitus, and senescence, to regulate its activity.

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饱和脂肪酸-和/或单不饱和脂肪酸-磷脂酸选择性地与磷酸甘油突变酶1相互作用并激活

本研究旨在鉴定由二酰基甘油激酶(DGKs) α、δ和ζ产生的16:0/16:0-磷脂酸（PA）的靶蛋白。我们发现磷酸甘油酸变化酶1 （PGAM1）是一个关键的糖酵解酶，它催化3-磷酸甘油酸转化为2-磷酸甘油酸，作为一种PA结合蛋白，与其他磷脂（包括磷脂酰肌醇、磷脂酰肌醇4-单磷酸、磷脂酰肌醇4,5-二磷酸、心磷脂、磷脂酰丝氨酸、磷脂酰甘油、磷脂酰胆碱和鞘磷脂）相比，对PA具有更强的亲和力。与含有多不饱和脂肪酸的PAs（如18:0/20:4-和18:0/22:6-PA）相比，PGAM1优先结合饱和脂肪酸(SFA)-和/或单不饱和脂肪酸(MUFA)- PAs，如16:0/16:0-，16:0/18:1-,18:0/18:0-，18:0/18:1-和18:1/18:1-PA。值得注意的是，16:0/16:0-和16:0/18:1-PA改变了PGAM1的二级构象，显著增强了其活性。有趣的是，PGAM1与DGKδ和ζ相互作用，但与DGKα不相互作用。这些发现表明SFA-和/或含mufa -的pas选择性地与PGAM1相互作用，以调节其活性，PGAM1是癌症、2型糖尿病和衰老的一个有希望的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

4.60

自引率

0.00%

发文量

191

审稿时长

59 days

期刊介绍： Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.