8IF8

Arabinosyltransferase AftA

Summary for 8IF8

• Entry DOI: 10.2210/pdb8if8/pdb
• EMDB information: 35410
• Descriptor: Galactan 5-O-arabinofuranosyltransferase, CALCIUM ION (2 entities in total)
• Functional Keywords: arabinosyltransferase, afta, mycobacterium tuberculosis, membrane protein
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 2
• Total formula weight: 139234.03

Authors

Gong, Y.C.,Rao, Z.H.,Zhang, L. (deposition date: 2023-02-17, release date: 2023-05-31, Last modification date: 2024-05-29)

Primary citation

Gong, Y.,Wei, C.,Wang, J.,Mu, N.,Lu, Q.,Wu, C.,Yan, N.,Yang, H.,Zhao, Y.,Yang, X.,Gurcha, S.S.,Veerapen, N.,Batt, S.M.,Hao, Z.,Da, L.,Besra, G.S.,Rao, Z.,Zhang, L.
Structure of the priming arabinosyltransferase AftA required for AG biosynthesis of Mycobacterium tuberculosis.
Proc.Natl.Acad.Sci.USA, 120:e2302858120-e2302858120, 2023

PubMed Abstract: Arabinogalactan (AG) is an essential cell wall component in mycobacterial species, including the deadly human pathogen . It plays a pivotal role in forming the rigid mycolyl-AG-peptidoglycan core for in vitro growth. AftA is a membrane-bound arabinosyltransferase and a key enzyme involved in AG biosynthesis which bridges the assembly of the arabinan chain to the galactan chain. It is known that AftA catalyzes the transfer of the first arabinofuranosyl residue from the donor decaprenyl-monophosphoryl-arabinose to the mature galactan chain (i.e., priming); however, the priming mechanism remains elusive. Herein, we report the cryo-EM structure of AftA. The detergent-embedded AftA assembles as a dimer with an interface maintained by both the transmembrane domain (TMD) and the soluble C-terminal domain (CTD) in the periplasm. The structure shows a conserved glycosyltransferase-C fold and two cavities converging at the active site. A metal ion participates in the interaction of TMD and CTD of each AftA molecule. Structural analyses combined with functional mutagenesis suggests a priming mechanism catalyzed by AftA in AG biosynthesis. Our data further provide a unique perspective into anti-TB drug discovery.

PubMed: 37252995
DOI: 10.1073/pnas.2302858120

Experimental method

ELECTRON MICROSCOPY (3.1 Å)