6PU3

ABC transporter-associated periplasmic binding protein DppA from Helicobacter pylori

6PU3 の概要

• エントリーDOI: 10.2210/pdb6pu3/pdb
• 関連するPDBエントリー: 6OFQ
• 分子名称: Heme-binding protein A, SER-THR-SER-ALA (3 entities in total)
• 機能のキーワード: dppa, type ii, periplasmic binding protein, periplasmic peptide binding protein, transport protein
• 由来する生物種: Helicobacter pylori; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60875.34

構造登録者

Rahman, M.M.,Machuca, M.A.,Khan, M.F.,Barlow, C.K.,Schittenhelm, R.B.,Roujeinikova, A. (登録日: 2019-07-16, 公開日: 2019-08-21, 最終更新日: 2023-10-11)

主引用文献

Rahman, M.M.,Machuca, M.A.,Khan, M.F.,Barlow, C.K.,Schittenhelm, R.B.,Roujeinikova, A.
Molecular Basis of Unexpected Specificity of ABC Transporter-Associated Substrate-Binding Protein DppA from Helicobacter pylori.
J.Bacteriol., 201:-, 2019

PubMed Abstract: The gastric pathogen has limited ability to use carbohydrates as a carbon source, relying instead on exogenous amino acids and peptides. Uptake of certain peptides by requires an ATP binding cassette (ABC) transporter annotated dipeptide permease (Dpp). The transporter specificity is determined by its cognate substrate-binding protein DppA, which captures ligands in the periplasm and delivers them to the permease. Here, we show that, unlike previously characterized DppA proteins, DppA binds, with micromolar affinity, peptides of diverse amino acid sequences ranging between two and eight residues in length. We present analysis of the 1.45-Å-resolution crystal structure of its complex with the tetrapeptide STSA, which provides a structural rationale for the observed broad specificity. Analysis of the molecular surface revealed a ligand-binding pocket that is large enough to accommodate peptides of up to nine residues in length. The structure suggests that DppA is able to recognize a wide range of peptide sequences by forming interactions primarily with the peptide main chain atoms. The loop that terminates the peptide-binding pocket in DppAs from other bacteria is significantly shorter in the protein, providing an explanation for its ability to bind longer peptides. The subsites accommodating the two N-terminal residues of the peptide ligand make the greatest contribution to the protein-ligand binding energy, in agreement with the observation that dipeptides bind with affinity close to that of longer peptides. The World Health Organization listed as a high-priority pathogen for antibiotic development. The potential of using peptide transporters in drug design is well recognized. We discovered that the substrate-binding protein of the ABC transporter for peptides, termed dipeptide permease, is an unusual member of its family in that it directly binds peptides of diverse amino acid sequences, ranging between two and eight residues in length. We also provided a structural rationale for the observed broad specificity. Since the ability to import peptides as a source of carbon is critical for , our findings will inform drug design strategies based on inhibition or fusion of membrane-impermeant antimicrobials with peptides.

PubMed: 31358613
DOI: 10.1128/JB.00400-19

実験手法

X-RAY DIFFRACTION (1.8 Å)