title: Structural analysis of PseH, the Campylobacter jejuni N-acetyltransferase involved in bacterial O-linked glycosylation.
abstract: Campylobacter jejuni is a bacterium that uses flagella for motility and causes worldwide acute gastroenteritis in humans. The C. jejuni N-acetyltransferase PseH (cjPseH) is responsible for the third step in flagellin O-linked glycosylation and plays a key role in flagellar formation and motility. cjPseH transfers an acetyl group from an acetyl donor, acetyl coenzyme A (AcCoA), to the amino group of UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine to produce UDP-2,4-diacetamido-2,4,6-trideoxy-β-L-altropyranose. To elucidate the catalytic mechanism of cjPseH, crystal structures of cjPseH alone and in complex with AcCoA were determined at 1.95 Å resolution. cjPseH folds into a single-domain structure of a central β-sheet decorated by four α-helices with two continuously connected grooves. A deep groove (groove-A) accommodates the AcCoA molecule. Interestingly, the acetyl end of AcCoA points toward an open space in a neighboring shallow groove (groove-S), which is occupied by extra electron density that potentially serves as a pseudosubstrate, suggesting that the groove-S may provide a substrate-binding site. Structure-based comparative analysis suggests that cjPseH utilizes a unique catalytic mechanism of acetylation that has not been observed in other glycosylation-associated acetyltransferases. Thus, our studies on cjPseH will provide valuable information for the design of new antibiotics to treat C. jejuni-induced gastroenteritis.
authors.affiliation: Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Wan Seok
authors.initials: WS
authors.lastname: Song
authors.affiliation: Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Nam
authors.affiliation: Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Byeol
authors.initials: B
authors.lastname: Namgung
authors.affiliation: Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Republic of Korea; Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea. Electronic address: sungil@kangwon.ac.kr.
authors.forename: Sung-il
authors.initials: SI
authors.lastname: Yoon
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000123:Acetyltransferases / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D016123:Campylobacter jejuni / Q000737:chemistry / Q000201:enzymology*; D018360:Crystallography, X-Ray; D006031:Glycosylation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment
chemical_list: D000105:Acetyl Coenzyme A; D000123:Acetyltransferases
keywords: Bacterial protein glycosylation; Campylobacter jejuni; Crystal structure; N-acetyltransferase; PseH