8J8K

Membrane bound PRTase, C3 symmetry, acceptor bound

Summary for 8J8K

• Entry DOI: 10.2210/pdb8j8k/pdb
• EMDB information: 36072
• Descriptor: Decaprenyl-phosphate phosphoribosyltransferase, MONO-TRANS, OCTA-CIS DECAPRENYL-PHOSPHATE (2 entities in total)
• Functional Keywords: phosphoribose transferase complex, membrane protein
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 3
• Total formula weight: 98152.91

Authors

Wu, F.Y.,Gao, S.,Zhang, L.,Rao, Z.H. (deposition date: 2023-05-01, release date: 2024-02-07, Last modification date: 2024-04-17)

Primary citation

Gao, S.,Wu, F.,Gurcha, S.S.,Batt, S.M.,Besra, G.S.,Rao, Z.,Zhang, L.
Structural analysis of phosphoribosyltransferase-mediated cell wall precursor synthesis in Mycobacterium tuberculosis.
Nat Microbiol, 9:976-987, 2024

PubMed Abstract: 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.

PubMed: 38491273
DOI: 10.1038/s41564-024-01643-8

Experimental method

ELECTRON MICROSCOPY (3.36 Å)