Crystal structure of an extracellular superoxide dismutase from Onchocerca volvulus and implications for parasite-specific drug development.
Cu/Zn superoxide dismutases
Onchocerca volvulus
X-ray crystallography
docking
drug targets
metal ion coordination
parasites
Journal
Acta crystallographica. Section F, Structural biology communications
ISSN: 2053-230X
Titre abrégé: Acta Crystallogr F Struct Biol Commun
Pays: United States
ID NLM: 101620319
Informations de publication
Date de publication:
01 Jun 2022
01 Jun 2022
Historique:
received:
05
04
2022
accepted:
19
05
2022
entrez:
1
6
2022
pubmed:
2
6
2022
medline:
7
6
2022
Statut:
ppublish
Résumé
Superoxide dismutases (SODs) are metalloproteins that are responsible for the dismutation of superoxide anion radicals. SODs are consequently protective against oxidative damage to cellular components. Among other protective mechanisms, the filarial parasite Onchocerca volvulus has a well developed defense system to scavenge toxic free radicals using SODs during migration and sojourning of the microfilariae and adult worms in the human body. O. volvulus is responsible for the neglected disease onchocerciasis or `river blindness'. In the present study, an extracellular Cu/Zn-SOD from O. volvulus (OvEC-SOD) was cloned, purified and crystallized to obtain structural insight into an attractive drug target with the potential to combat onchocerciasis. The recombinant OvEC-SOD forms a dimer and the protein structure was solved and refined to 1.55 Å resolution by X-ray crystallography. Interestingly, a sulfate ion supports the coordination of the conserved copper ion. The overall protein shape was verified by small-angle X-ray scattering. The enzyme shows a different surface charge distribution and different termini when compared with the homologous human SOD. A distinct hydrophobic cleft to which both protomers of the dimer contribute was utilized for a docking approach with compounds that have previously been identified as SOD inhibitors to highlight the potential for individual structure-based drug development.
Identifiants
pubmed: 35647680
pii: S2053230X22005350
doi: 10.1107/S2053230X22005350
pmc: PMC9158661
doi:
Substances chimiques
Superoxide Dismutase
EC 1.15.1.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
232-240Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : EXC 2056 - project ID 390715994
Organisme : Deutsche Forschungsgemeinschaft
ID : PAK296
Organisme : Deutscher Akademischer Austauschdienst
ID : A/11/92506
Informations de copyright
open access.
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