6BQS

HusA haemophore from Porphyromonas gingivalis


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 21 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural properties of a haemophore facilitate targeted elimination of the pathogen Porphyromonas gingivalis.

Gao, J.L.Kwan, A.H.Yammine, A.Zhou, X.Trewhella, J.Hugrass, B.M.Collins, D.A.T.Horne, J.Ye, P.Harty, D.Nguyen, K.A.Gell, D.A.Hunter, N.

(2018) Nat Commun 9: 4097-4097

  • DOI: https://doi.org/10.1038/s41467-018-06470-0
  • Primary Citation of Related Structures:  
    6BQS, 6CRL

  • PubMed Abstract: 

    Porphyromonas gingivalis is a keystone bacterial pathogen of chronic periodontitis. P. gingivalis is unable to synthesise the porphyrin macrocycle and relies on exogenous porphyrin, including haem or haem biosynthesis intermediates from host sources. We show that under the iron-limited conditions prevailing in tissue environments, P. gingivalis expresses a haemophore-like protein, HusA, to mediate the uptake of essential porphyrin and support pathogen survival within epithelial cells. The structure of HusA, together with titration studies, mutagenesis and in silico docking, show that haem binds in a hydrophobic groove on the α-helical structure without the typical iron coordination seen in other haemophores. This mode of interaction allows HusA to bind to a variety of abiotic and metal-free porphyrins with higher affinities than to haem. We exploit this unusual porphyrin-binding activity of HusA to target a prototypic deuteroporphyrin-metronidazole conjugate with restricted antimicrobial specificity in a Trojan horse strategy that effectively kills intracellular P. gingivalis.


  • Organizational Affiliation

    School of Dentistry, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, 2145, Australia. jinlong.gao@sydney.edu.au.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
hypothetical protein PG_2227201Porphyromonas gingivalis W83Mutation(s): 0 
Gene Names: PG_2227
UniProt
Find proteins for Q7MSY3 (Porphyromonas gingivalis (strain ATCC BAA-308 / W83))
Explore Q7MSY3 
Go to UniProtKB:  Q7MSY3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ7MSY3
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 21 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-10-10
    Type: Initial release
  • Version 1.1: 2018-10-17
    Changes: Data collection, Database references, Structure summary
  • Version 1.2: 2024-05-01
    Changes: Data collection, Database references