7WX5

a Legionella acetyltransferase effector VipF

Replaces:  7C4E

Summary for 7WX5

• Entry DOI: 10.2210/pdb7wx5/pdb
• Descriptor: N-acetyltransferase, ACETYL COENZYME *A (3 entities in total)
• Functional Keywords: toxin, acetyltransferase, transferase
• Biological source: Legionella pneumophila
• Total number of polymer chains: 1
• Total formula weight: 36776.44

Authors

Chen, T.T.,Lin, Y.L.,Zhang, S.J.,Han, A.D. (deposition date: 2022-02-14, release date: 2023-02-22, Last modification date: 2024-04-03)

Primary citation

Chen, T.T.,Lin, Y.,Zhang, S.,Han, A.
Structural basis for the acetylation mechanism of the Legionella effector VipF.
Acta Crystallogr D Struct Biol, 78:1110-1119, 2022

PubMed Abstract: 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 β-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.

PubMed: 36048151
DOI: 10.1107/S2059798322007318

Experimental method

X-RAY DIFFRACTION (2.392 Å)