Complexes formed by the siderophore-based monosulfactam antibiotic BAL30072 and their interaction with the outer membrane receptor PiuA of P. aeruginosa.
Biometals
; 32(1): 155-170, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30635814
ABSTRACT
Nuclear magnetic resonance and infrared spectroscopy have been used to investigate the formation of complexes of BAL30072 with Fe3+ and Ga3+ in solution and to collect geometrical parameters supporting reliable 3D structure models. Structural models for the ligand-metal complexes with different stoichiometries have been characterized using density functional theory calculations. Blind ensemble docking to the PiuA receptor from P. aeruginosa was performed for the different complexes to compare binding affinities and statistics of the residues most frequently contacted. When compared to analogues, BAL30072 was found to have an intrinsic propensity to form complexes with low ligand-to-metal stoichiometry. By using one of the sulfate oxygen atoms as a third donor in addition to the bidentate pyridinone moiety, BAL30072 can form a L2M complex, which was predicted to be the one with the best binding affinity to PiuA. The example of BAL30072 strongly suggests that a lower stoichiometry might be the one recognized by the receptor, so that to focus only on the highest stoichiometry might be misleading for siderophores with less than six donors.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
/
Tiazóis
/
Proteínas da Membrana Bacteriana Externa
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Monobactamas
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Sideróforos
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Antibacterianos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Biometals
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália