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1.
ACS Omega ; 7(23): 19898-19912, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35721994

RESUMO

Terpenoids form a large pool of highly diverse organic compounds possessing several economically important properties, including nutritional, aromatic, and pharmacological properties. The 1-deoxy-d-xylulose 5-phosphate (DXP) pathway's end enzyme, nuclear distribution protein (NudF), interacting with isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), is critical for the synthesis of isoprenol/prenol/downstream compounds. The enzyme is yet to be thoroughly investigated to increase the overall yield of terpenoids in the Bacillus subtilis, which is widely used in industry and is generally regarded as a safe (GRAS) bacterium. The study aims to analyze the evolutionary conservation across the active site for mapping the key residues for mutagenesis studies. The 37-sequence data set, extracted from 103 Bacillus subtilis entries, shows a high phylogenetic divergence, and only six one-motif sequences ASB92783.1, ASB69297.1, ASB56714.1, AOR97677.1, AOL97023.1, and OAZ71765.1 show a monophyly relationship, unlike a complete polyphyly relationship between the other 31 three-motif sequences. Furthermore, only 47 of 179 residues of the representative sequence CUB50584.1 are observed to be significantly conserved. Docking analysis suggests a preferential bias of adenosine diphosphate (ADP)-ribose pyrophosphatase toward IPP, and a nearly threefold energetic difference is observed between IPP and DMAPP. The loops are hereby shown to play a regulatory role in guiding the promiscuity of NudF toward a specific ligand. Computational saturation mutagenesis of the seven hotspot residues identifies two key positions LYS78 and PHE116, orderly encoded within loop1 and loop7, majorly interacting with the ligands DMAPP and IPP, and their mutants K78I/K78L and PHE116D/PHE116E are found to stabilize the overall conformation. Molecular dynamics analysis shows that the IPP complex is significantly more stable than the DMAPP complex, and the NudF structure is very unstable. Besides showing a promiscuous binding of NudF with ligands, the analysis suggests its rate-limiting nature. The study would allow us to customize the metabolic load toward the synthesis of any of the downstream molecules. The findings would pave the way for the development of catalytically improved NudF mutants for the large-scale production of specific terpenoids with significant nutraceutical or commercial value.

2.
J Pharm Bioallied Sci ; 12(Suppl 1): S14-S19, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33149425

RESUMO

Titanium and its alloys are mainly used in manufacturing dental implants. The fact that titanium implants are immunologically very effective, new methods are being experimented to achieve utmost success rate as a biomaterial. One fundamental indicator for clinical achievement of implant is the decision of composition decided for the implant with the objective to improve osseointegration. The main objective of this study was to explore literature on dental materials used for implants, contrast them with titanium dental implants, with the aim to improve osseointegration and mechanical quality using Ti-Ga-Si dental implant.

3.
J Pharm Bioallied Sci ; 12(Suppl 1): S289-S294, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33149473

RESUMO

OBJECTIVE: The postoperative symptoms after third molar removal surgery were commonly uneventful. The aim of this study was to compare two proteolytic enzymes from different origin and to prove which enzyme provides a faster healing. One of the proteolytic enzymes involves a combination with a flavonoid. This involves trypsin, bromelain, along with a flavonoid rutin. Another proteolytic enzyme is serratiopeptidase that helps in degradation of insoluble proteins causing reduced swelling in the operated site. MATERIALS AND METHODS: In this study, voluntary subjects of clinically indicated bilateral lower third impaction were selected. The subjects were recommended to undergo extraction of impacted teeth in two sittings, one extraction per visit. In the first sitting, subjects were prescribed trypsin, bromelain, and rutin combination after removal of 48 teeth and in the second sitting subjects were prescribed serratiopeptidase after removal of 38 teeth. There was a time interval of 2-3 weeks in between the sittings. The post findings such as mouth opening, swelling, and pain scale were noted. RESULTS: The results showed that the proteolytic enzyme combination of trypsin, bromelain, and rutin is better than serratiopeptidase. CONCLUSION: It is recommended that trypsin, bromelain, and rutin combination can be used effectively for postoperative purpose to facilitate wound healing.

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