8TV8
Crystal structure of nontypeable Haemophilus influenzae SapA
Summary for 8TV8
| Entry DOI | 10.2210/pdb8tv8/pdb |
| Descriptor | ABC-type transport system, periplasmic component, involved in antimicrobial peptide resistance (2 entities in total) |
| Functional Keywords | peptide binding protein |
| Biological source | Haemophilus influenzae 86-028NP |
| Total number of polymer chains | 1 |
| Total formula weight | 64492.11 |
| Authors | Tanaka, K.J.,Buechel, E.R.,Rivera, K.G.,Pinkett, H.W. (deposition date: 2023-08-17, release date: 2024-01-17, Last modification date: 2024-11-13) |
| Primary citation | 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 Cited by 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: 38189237DOI: 10.1021/acs.biochem.3c00562 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
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