Kinetic and thermodynamic characterisation of HIV-protease inhibitors against E35D↑G↑S mutant in the South African HIV-1 subtype C protease.


Journal

Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203

Informations de publication

Date de publication:
Dec 2019
Historique:
entrez: 15 8 2019
pubmed: 15 8 2019
medline: 27 8 2019
Statut: ppublish

Résumé

Herein, we report the effect of nine FDA approved protease inhibitor drugs against a new HIV-1 subtype C mutant protease, E35D↑G↑S. The mutant has five mutations, E35D, two insertions, position 36 (G and S), and D60E. Kinetics, inhibition constants, vitality, Gibbs free binding energies are reported. The variant showed a decreased affinity for substrate and low catalytic efficiency compared to the wild type. There was a significant decrease in the binding of seven FDA approved protease inhibitors against the mutant (

Identifiants

pubmed: 31409143
doi: 10.1080/14756366.2019.1636234
pmc: PMC6713120
doi:

Substances chimiques

HIV Protease Inhibitors 0
HIV Protease EC 3.4.23.-
p16 protease, Human immunodeficiency virus 1 EC 3.4.23.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1451-1456

Références

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Auteurs

Sibusiso Maseko (S)

a Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal , Durban , South Africa.

Eden Padayachee (E)

a Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal , Durban , South Africa.

Siyabonga Maphumulo (S)

a Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal , Durban , South Africa.

Thavendran Govender (T)

a Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal , Durban , South Africa.

Yasien Sayed (Y)

b Protein Structure-Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand , Wits , South Africa.

Glenn Maguire (G)

a Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal , Durban , South Africa.
c School of Chemistry and Physics, University of KwaZulu-Natal , Durban , South Africa.

Johnson Lin (J)

d School of Life Sciences, University of KwaZulu-Natal , Durban , South Africa.

Tricia Naicker (T)

a Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal , Durban , South Africa.

Sooraj Baijnath (S)

a Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal , Durban , South Africa.

Kruger Hendrik Gerhardus (KH)

a Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal , Durban , South Africa.

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Classifications MeSH