PDBsum entry 4bet

Transferase

PDB id: 4bet

Contents

Protein chains

480 a.a.

Ligands

CDC ×2

SO4 ×4

GOL ×3

Waters ×114

PDB id:

4bet

Name:

Transferase

Title:

Crystal structure of the legionella pneumophila fic domain-containing effector ankx protein (inactive h229a mutant) in complex with cytidine-diphosphate-choline

Structure:

Phosphocholine transferase ankx. Chain: a, b. Fragment: fic and ankyrin repeats domains, residues 2-484. Synonym: pc transferase, ankyrin repeat-containing protein x. Engineered: yes. Mutation: yes. Other_details: inactive mutant

Source:

Legionella pneumophila. Organism_taxid: 446. Strain: philadelphia 1. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta plyss.

Resolution:

2.55Å R-factor: 0.206 R-free: 0.247

Authors:

V.Campanacci,S.Mukherjee,C.R.Roy,J.Cherfils

Key ref:

V.Campanacci et al. (2013). Structure of the Legionella effector AnkX reveals the mechanism of phosphocholine transfer by the FIC domain. Embo J, 32, 1469-1477. PubMed id: 23572077 DOI: 10.1038/emboj.2013.82

Date:

12-Mar-13 Release date: 24-Apr-13

Protein chains

Q5ZXN6  (ANKX_LEGPH) -  Phosphocholine transferase AnkX from Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513)

Seq: 949 a.a.

Struc: 480 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.1.- - ?????

DOI no: 10.1038/emboj.2013.82

Embo J 32:1469-1477 (2013)

PubMed id: 23572077

Structure of the Legionella effector AnkX reveals the mechanism of phosphocholine transfer by the FIC domain.

V.Campanacci, S.Mukherjee, C.R.Roy, J.Cherfils.

ABSTRACT

The FIC motif and the eukaryotic-like ankyrin repeats are found in many bacterial type IV effectors, yet little is known about how these domains enable bacteria to modulate host cell functions. Bacterial FIC domains typically bind ATP and transfer adenosine monophosphate moiety onto target proteins. The ankyrin repeat-containing protein AnkX encoded by the intracellular pathogen Legionella pneumophila is unique in that its FIC domain binds to CDP-choline and transfers a phosphocholine residue onto proteins in the Rab1 GTPase family. By determining the structures of unbound AnkX and AnkX with bound CDP-choline, CMP/phosphocholine and CMP, we demonstrate that the orientation of substrate binding in relation to the catalytic FIC motif enables this protein to function as a phosphocholinating enzyme rather than a nucleotidyl transferase. Additionally, the structure reveals that the ankyrin repeats mediate scaffolding interactions that resemble those found in protein-protein interactions, but are unprecedented in intramolecular interactions. Together with phosphocholination experiments, our structures unify a general phosphoryl transferase mechanism common to all FIC enzymes that should be conserved from bacteria to human.