Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients.
Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients.
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DOI：
10.1038/s41467-022-29836-x
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发表时间：
2022-04-27
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
通过肽聚糖（PG）维持细菌细胞形状和对渗透胁迫的抗性使得PG生物合成酶和前体成为对抗细菌感染的有吸引力的靶标。在这里，通过应用本机质谱，我们阐明了PG膜酶MraY，MurG和MurJ的脂质底物的影响。我们表明，MraY的二聚化是与结合的载体脂质底物磷酸十一异戊二烯酯（C55-P）。此外，我们证明了使用本地MS的生物合成反应监测，并发现通过的基板和产品是由不同的膜酶的相对结合亲和力控制。总体而言，我们提供了一个PG膜酶如何通过有利的结合事件传递脂质前体的分子观点，并强调可能的干预机会。细菌细胞壁酶及其前体是抗生素开发的关键目标。在这里，作者研究了几种生物合成酶及其底物，并表明底物和产物在途径中的通过受其相对结合亲和力的控制。
Maintenance of bacterial cell shape and resistance to osmotic stress by the peptidoglycan (PG) renders PG biosynthetic enzymes and precursors attractive targets for combating bacterial infections. Here, by applying native mass spectrometry, we elucidate the effects of lipid substrates on the PG membrane enzymes MraY, MurG, and MurJ. We show that dimerization of MraY is coupled with binding of the carrier lipid substrate undecaprenyl phosphate (C55-P). Further, we demonstrate the use of native MS for biosynthetic reaction monitoring and find that the passage of substrates and products is controlled by the relative binding affinities of the different membrane enzymes. Overall, we provide a molecular view of how PG membrane enzymes convey lipid precursors through favourable binding events and highlight possible opportunities for intervention. Bacterial cell wall enzymes and their precursors are critical targets for antibiotic development. Here, the authors investigate several biosynthetic enzymes with their substrates and show that the passage of substrates and products in the pathway is controlled by their relative binding affinities.
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影响因子：
2.1
作者：
Kramer, NE;Smid, EJ;Breukink, E
通讯作者：
Breukink, E
影响因子：
64.8
作者：
Chung BC;Mashalidis EH;Tanino T;Kim M;Matsuda A;Hong J;Ichikawa S;Lee SY
通讯作者：
Lee SY
DOI：
10.1126/science.1236501
发表时间：
2013-08-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chung BC;Zhao J;Gillespie RA;Kwon DY;Guan Z;Hong J;Zhou P;Lee SY
通讯作者：
Lee SY
影响因子：
8
作者：
Ha, S;Walker, D;Walker, S
通讯作者：
Walker, S
影响因子：
5.5
作者：
Best, Robert B.;Zhu, Xiao;Shim, Jihyun;Lopes, Pedro E. M.;Mittal, Jeetain;Feig, Michael;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.