2PZL

Crystal structure of the Bordetella bronchiseptica enzyme WbmG in complex with NAD and UDP

2PZL の概要

• エントリーDOI: 10.2210/pdb2pzl/pdb
• 関連するPDBエントリー: 2PZK
• 分子名称: Putative nucleotide sugar epimerase/ dehydratase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, URIDINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: rossmann fold, protein-nad complex, protein-nucleotide complex, sugar binding protein
• 由来する生物種: Bordetella bronchiseptica
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 72711.14

構造登録者

King, J.D.,Harmer, N.J.,Maskell, D.J.,Blundell, T.L. (登録日: 2007-05-18, 公開日: 2007-10-02, 最終更新日: 2023-08-30)

主引用文献

King, J.D.,Harmer, N.J.,Preston, A.,Palmer, C.M.,Rejzek, M.,Field, R.A.,Blundell, T.L.,Maskell, D.J.
Predicting protein function from structure--the roles of short-chain dehydrogenase/reductase enzymes in Bordetella O-antigen biosynthesis.
J.Mol.Biol., 374:749-763, 2007

PubMed Abstract: The pathogenic bacteria Bordetella parapertussis and Bordetella bronchiseptica express a lipopolysaccharide O antigen containing a polymer of 2,3-diacetamido-2,3-dideoxy-l-galacturonic acid. The O-antigen cluster contains three neighbouring genes that encode proteins belonging to the short-chain dehydrogenase/reductase (SDR) family, wbmF, wbmG and wbmH, and we aimed to elucidate their individual functions. Mutation and complementation implicate each gene in O-antigen expression but, as their putative sugar nucleotide substrates are not currently available, biochemical characterisation of WbmF, WbmG and WbmH is impractical at the present time. SDR family members catalyse a wide range of chemical reactions including oxidation, reduction and epimerisation. Because they typically share low sequence conservation, however, catalytic function cannot be predicted from sequence analysis alone. In this context, structural characterisation of the native proteins, co-crystals and small-molecule soaks enables differentiation of the functions of WbmF, WbmG and WbmH. These proteins exhibit typical SDR architecture and coordinate NAD. In the substrate-binding domain, all three enzymes bind uridyl nucleotides. WbmG contains a typical SDR catalytic TYK triad, which is required for oxidoreductase function, but the active site is devoid of additional acid-base functionality. Similarly, WbmH possesses a TYK triad, but an otherwise feature-poor active site. Consequently, 3,5-epimerase function can probably be ruled out for these enzymes. The WbmF active site contains conserved 3,5-epimerase features, namely, a positionally conserved cysteine (Cys133) and basic side chain (His90 or Asn213), but lacks the serine/threonine component of the SDR triad and therefore may not act as an oxidoreductase. The data suggest a pathway for synthesis of the O-antigen precursor UDP-2,3-diacetamido-2,3-dideoxy-l-galacturonic acid and illustrate the usefulness of structural data in predicting protein function.

PubMed: 17950751
DOI: 10.1016/j.jmb.2007.09.055

実験手法

X-RAY DIFFRACTION (2.39 Å)