8TV8

Crystal structure of nontypeable Haemophilus influenzae SapA

8TV8 の概要

• エントリーDOI: 10.2210/pdb8tv8/pdb
• 分子名称: ABC-type transport system, periplasmic component, involved in antimicrobial peptide resistance (2 entities in total)
• 機能のキーワード: peptide binding protein
• 由来する生物種: Haemophilus influenzae 86-028NP
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 64492.11

構造登録者

Tanaka, K.J.,Buechel, E.R.,Rivera, K.G.,Pinkett, H.W. (登録日: 2023-08-17, 公開日: 2024-01-17, 最終更新日: 2024-11-13)

主引用文献

Rivera, K.G.,Tanaka, K.J.,Buechel, E.R.,Origel Jr., O.,Harrison, A.,Mason, K.M.,Pinkett, H.W.
Antimicrobial Peptide Recognition Motif of the Substrate Binding Protein SapA from Nontypeable Haemophilus influenzae .
Biochemistry, 63:294-311, 2024

PubMed Abstract: Nontypeable (NTHi) is an opportunistic pathogen associated with respiratory diseases, including otitis media and exacerbations of chronic obstructive pulmonary disease. NTHi exhibits resistance to killing by host antimicrobial peptides (AMPs) mediated by SapA, the substrate binding protein of the ensitivity to ntimicrobial eptides (Sap) transporter. However, the specific mechanisms by which SapA selectively binds various AMPs such as defensins and cathelicidin are unknown. In this study, we report mutational analyses of both defensin AMPs and the SapA binding pocket to define the specificity of AMP recognition. Bactericidal assays revealed that NTHi lacking SapA are more susceptible to human beta defensins and LL-37, while remaining highly resistant to a human alpha defensin. In contrast to homologues, our research underscores the distinct specificity of NTHi SapA, which selectively recognizes and binds to peptides containing the charged-hydrophobic motif PKE and RRY. These findings provide valuable insight into the divergence of SapA among bacterial species and NTHi SapA's ability to selectively interact with specific AMPs to mediate resistance.

PubMed: 38189237
DOI: 10.1021/acs.biochem.3c00562

実験手法

X-RAY DIFFRACTION (2.25 Å)