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蛋白羧甲基转移酶依赖的天冬氨酸挽救途径在 的复杂代谢网络中起着至关重要的作用。

The protein carboxymethyltransferase-dependent aspartate salvage pathway plays a crucial role in the intricate metabolic network of .

机构信息

Institut Cochin, Université Paris Cité, INSERM U1016, CNRS UMR 8104, 75014 Paris, France.

IAME, Université de Paris, INSERM U1137, Université Sorbonne Paris Nord, 75018 Paris, France.

出版信息

Sci Adv. 2024 Feb 9;10(6):eadj0767. doi: 10.1126/sciadv.adj0767.

DOI:10.1126/sciadv.adj0767
PMID:38335294
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10857468/
Abstract

Protein carboxymethyltransferase (Pcm) is a highly evolutionarily conserved enzyme that initiates the conversion of abnormal isoaspartate to aspartate residues. While it is commonly believed that Pcm facilitates the repair of damaged proteins, a number of observations suggest that it may have another role in cell functioning. We investigated whether Pcm provides a means for to recycle aspartate, which is essential for protein synthesis and other cellular processes. We showed that Pcm is required for the energy production, the maintenance of cellular redox potential and of -adenosylmethionine synthesis, which are critical for the proper functioning of many metabolic pathways. Pcm contributes to the full growth capacity both under aerobic and anaerobic conditions. Last, we showed that Pcm enhances the robustness of bacteria when exposed to sublethal antibiotic treatments and improves their fitness in the mammalian urinary tract. We propose that Pcm plays a crucial role in metabolism by ensuring a steady supply of aspartate.

摘要

蛋白羧甲基转移酶（Pcm）是一种高度进化保守的酶，它启动将异常异天冬氨酸转化为天冬氨酸残基的过程。虽然普遍认为 Pcm 有助于修复受损的蛋白质，但有许多观察结果表明它在细胞功能中可能具有另一种作用。我们研究了 Pcm 是否为提供一种用于回收天冬氨酸的途径，因为天冬氨酸是蛋白质合成和其他细胞过程所必需的。我们表明 Pcm 对于能量产生、细胞氧化还原电位的维持和 -腺苷甲硫氨酸的合成是必需的，这些对于许多代谢途径的正常功能至关重要。Pcm 有助于在有氧和无氧条件下充分发挥生长能力。最后，我们表明 Pcm 增强了细菌在亚致死抗生素处理下的稳健性，并提高了它们在哺乳动物泌尿道中的适应性。我们提出 Pcm 通过确保天冬氨酸的稳定供应在代谢中发挥关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f9/10857468/f1667e9bdc3c/sciadv.adj0767-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f9/10857468/ad423cf8076b/sciadv.adj0767-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f9/10857468/f2ea9c748e15/sciadv.adj0767-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f9/10857468/d6e8db20cc7a/sciadv.adj0767-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f9/10857468/8aa14ac4ea64/sciadv.adj0767-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f9/10857468/6e325acf280b/sciadv.adj0767-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f9/10857468/f1667e9bdc3c/sciadv.adj0767-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f9/10857468/ad423cf8076b/sciadv.adj0767-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f9/10857468/f2ea9c748e15/sciadv.adj0767-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f9/10857468/d6e8db20cc7a/sciadv.adj0767-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f9/10857468/8aa14ac4ea64/sciadv.adj0767-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f9/10857468/6e325acf280b/sciadv.adj0767-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f9/10857468/f1667e9bdc3c/sciadv.adj0767-f6.jpg

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