Structural analysis of phosphoribosyltransferase-mediated cell wall precursor synthesis in Mycobacterium tuberculosis
2024-03
发表期刊NATURE MICROBIOLOGY (IF:20.5[JCR-2023],21.0[5-Year])
ISSN20585276
发表状态已发表
DOI10.1038/s41564-024-01643-8
摘要

In Mycobacterium tuberculosis, Rv3806c is a membrane-bound
phosphoribosyltransferase (PRTase) involved in cell wall precursor
production. It catalyses pentosyl phosphate transfer from phosphoribosyl
pyrophosphate to decaprenyl phosphate, to generate 5-phospho-β-ribosyl-
1-phosphoryldecaprenol. Despite Rv3806c being an attractive drug
target, structural and molecular mechanistic insight into this PRTase is
lacking. Here we report cryogenic electron microscopy structures for
Rv3806c in the donor- and acceptor-bound states. In a lipidic environment,
Rv3806c is trimeric, creating a UbiA-like fold. Each protomer forms
two helical bundles, which, alongside the bound lipids, are required for
PRTase activity in vitro. Mutational and functional analyses reveal that
decaprenyl phosphate and phosphoribosyl pyrophosphate bind the
intramembrane and extramembrane cavities of Rv3806c, respectively,
in a distinct manner to that of UbiA superfamily enzymes. Our data suggest
a model for Rv3806c-catalysed phosphoribose transfer through an
inverting mechanism. These findings provide a structural basis for cell
wall precursor biosynthesis that could have potential for anti-tuberculosis
drug development.

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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/354906
专题免疫化学研究所_特聘教授组_饶子和组
免疫化学研究所_PI研究组_张璐组
共同第一作者Wu FY(吴方羽)
通讯作者Gao S(高珊); Zhang L(张璐)
作者单位
1.南开大学
2.上海科技大学
通讯作者单位上海科技大学
推荐引用方式
GB/T 7714
Gao S,Wu FY,Rao ZH,et al. Structural analysis of phosphoribosyltransferase-mediated cell wall precursor synthesis in Mycobacterium tuberculosis[J]. NATURE MICROBIOLOGY,2024.
APA Gao S,Wu FY,Rao ZH,&Zhang L.(2024).Structural analysis of phosphoribosyltransferase-mediated cell wall precursor synthesis in Mycobacterium tuberculosis.NATURE MICROBIOLOGY.
MLA Gao S,et al."Structural analysis of phosphoribosyltransferase-mediated cell wall precursor synthesis in Mycobacterium tuberculosis".NATURE MICROBIOLOGY (2024).
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