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Publication Abstract from PubMed

The pathogen Legionella pneumophila, which is the causative agent of Legionnaires' disease, secrets hundreds of effectors into host cells via its Dot/Icm secretion system to subvert host-cell pathways during pathogenesis. VipF, a conserved core effector among Legionella species, is a putative acetyltransferase, but its structure and catalytic mechanism remain unknown. Here, three crystal structures of VipF in complex with its cofactor acetyl-CoA and/or a substrate are reported. The two GNAT-like domains of VipF are connected as two wings by two beta-strands to form a U-shape. Both domains bind acetyl-CoA or CoA, but only in the C-terminal domain does the molecule extend to the bottom of the U-shaped groove as required for an active transferase reaction; the molecule in the N-terminal domain folds back on itself. Interestingly, when chloramphenicol, a putative substrate, binds in the pocket of the central U-shaped groove adjacent to the N-terminal domain, VipF remains in an open conformation. Moreover, mutations in the central U-shaped groove, including Glu129 and Asp251, largely impaired the acetyltransferase activity of VipF, suggesting a unique enzymatic mechanism for the Legionella effector VipF.

Structural basis for the acetylation mechanism of the Legionella effector VipF.,Chen TT, Lin Y, Zhang S, Han A Acta Crystallogr D Struct Biol. 2022 Sep 1;78(Pt 9):1110-1119. doi:, 10.1107/S2059798322007318. Epub 2022 Aug 9. PMID:36048151^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.