Crystallographic study of the phosphoethanolamine transferase EptC required for polymyxin resistance and motility in Campylobacter jejuni. (1st October 2014)

• Record Type: Journal Article
• Authors: Fage, Christopher D.; Brown, Dusty B.; Boll, Joseph M.; Keatinge‐Clay, Adrian T.; Trent, M. Stephen
• Is Part Of: Acta crystallographica. Volume 70:Part 10(2014:Oct.)
• Page Start: 2730
• Page End: 2739
• Publication Date: 2014-10-01
• Subjects: Biomolecules -- Structure -- Periodicals; Physical biochemistry -- Periodicals; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; 572
• DOI: 10.1107/S1399004714017623
• Languages: English
• ISSNs: 0907-4449

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The foodborne enteric pathogen <italic>Campylobacter jejuni</italic> decorates a variety of its cell‐surface structures with phosphoethanolamine (pEtN). Modifying lipid A with pEtN promotes cationic antimicrobial peptide resistance, whereas post‐translationally modifying the flagellar rod protein FlgG with pEtN promotes flagellar assembly and motility, which are processes that are important for intestinal colonization. EptC, the pEtN transferase required for all known pEtN cell‐surface modifications in <italic>C. jejuni</italic>, is a predicted inner‐membrane metalloenzyme with a five‐helix N‐terminal transmembrane domain followed by a soluble sulfatase‐like catalytic domain in the periplasm. The atomic structure of the catalytic domain of EptC (cEptC) was crystallized and solved to a resolution of 2.40 Å. cEptC adopts the α/β/α fold of the sulfatase protein family and harbors a zinc‐binding site. A phosphorylated Thr266 residue was observed that was hypothesized to mimic a covalent pEtN–enzyme intermediate. The requirement for Thr266 as well as the nearby residues Asn308, Ser309, His358 and His440 was ascertained <italic>via in vivo</italic> activity assays on mutant strains. The results establish a basis for the design of pEtN transferase inhibitors.</p> </abstract>