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Ann Clin Microbiol Antimicrob. 2018 Apr 2;17(1):16. doi: 10.1186/s12941-018-0266-9.

Ginger (Zingiber officinale) phytochemicals-gingerenone-A and shogaol inhibit SaHPPK: molecular docking, molecular dynamics simulations and in vitro approaches.

Author information

1
Division of Applied Life Science (BK21 Plus Program), Systems and Synthetic Agrobiotech Center (SSAC), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science (RINS), Gyeongsang National University, Jinju, 52828, Republic of Korea.
2
Primer Biotech Research Center, Jaipuri Colony, Nagole, Hyderabad, Telangana, 500068, India.
3
Department of Science Education, Kyungnam University, Changwon, 51767, Republic of Korea.
4
Department of Chemical Engineering, Kangwon National University, Chunchon, 24341, Republic of Korea.
5
Division of Applied Life Science (BK21 Plus Program), Systems and Synthetic Agrobiotech Center (SSAC), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science (RINS), Gyeongsang National University, Jinju, 52828, Republic of Korea. kwlee@gnu.ac.kr.

Abstract

BACKGROUND:

Antibiotic resistance is a defense mechanism, harbored by pathogens to survive under unfavorable conditions. Among several antibiotic resistant microbial consortium, Staphylococcus aureus is one of the most havoc microorganisms. Staphylococcus aureus encodes a unique enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (SaHPPK), against which, none of existing antibiotics have been reported.

METHODS:

Computational approaches have been instrumental in designing and discovering new drugs for several diseases. The present study highlights the impact of ginger phytochemicals on Staphylococcus aureus SaHPPK. Herein, we have retrieved eight ginger phytochemicals from published literature and investigated their inhibitory interactions with SaHPPK. To authenticate our work, the investigation proceeds considering the known antibiotics alongside the phytochemicals. Molecular docking was performed employing GOLD and CDOCKER. The compounds with the highest dock score from both the docking programmes were tested for their inhibitory capability in vitro. The binding conformations that were seated within the binding pocket showing strong interactions with the active sites residues rendered by highest dock score were forwarded towards the molecular dynamic (MD) simulation analysis.

RESULTS:

Based on molecular dock scores, molecular interaction with catalytic active residues and MD simulations studies, two ginger phytochemicals, gingerenone-A and shogaol have been proposed as candidate inhibitors against Staphylococcus aureus. They have demonstrated higher dock scores than the known antibiotics and have represented interactions with the key residues within the active site. Furthermore, these compounds have rendered considerable inhibitory activity when tested in vitro. Additionally, their superiority was corroborated by stable MD results conducted for 100 ns employing GROMACS package.

CONCLUSIONS:

Finally, we suggest that gingerenone-A and shogaol may either be potential SaHPPK inhibitors or can be used as fundamental platforms for novel SaHPPK inhibitor development.

KEYWORDS:

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase; GOLD; Ginger phytochemicals; Gingerenone-A; MD simulations; Shogaol

PMID:
29609660
PMCID:
PMC5879566
DOI:
10.1186/s12941-018-0266-9
[Indexed for MEDLINE]
Free PMC Article

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