In silico study of binding motifs in squalene synthase enzyme of secondary metabolic pathway solanaceae family

Sanchita, .; Singh, Garima; Sharma, Ashok

doi:10.1007/s11033-014-3603-x

Cited by 6 publications

(9 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this regard, our findings are in line with the results previously reported in SQS of ginseng species [41] and W. somnifera [38] that the distribution of alpha helix and random coils are comparatively higher. The secondary structure of SQS was also predicted by the PSIPRED, Protein Structure Prediction Server (PSIPRED V3.3) which verified SOPMA results.…”

Section: Resultssupporting

confidence: 93%

“…These conserved motifs were present in all proteins considered for the study. According to previous reports, these motifs sequences are found in different plants with numerous residues replacement [36], [37], [38], [39]. Regarding the sequence of protein in all Fabaceae plants, there were two ranges of 168–183 and 201–229 for the motifs’ positions in motif 1 and 2, respectively.…”

Section: Resultsmentioning

confidence: 77%

“…Regarding the sequence of protein in all Fabaceae plants, there were two ranges of 168–183 and 201–229 for the motifs’ positions in motif 1 and 2, respectively. These positions are the same reported in W. somnifera [38]. These two conserved motifs were considered to design the universal degenerate primers.…”

Section: Resultsmentioning

confidence: 98%

See 2 more Smart Citations

In silico analysis of squalene synthase in Fabaceae family using bioinformatics tools

Aminfar

Tohidfar

2018

Journal of Genetic Engineering and Biotechnology

View full text Add to dashboard Cite

Triterpenoid saponins are a diverse group of bioactive compounds, which are used for possessing of many biomedical and pharmaceutical products. Generally, squalene synthase (SQS) is defined as an emerging and essential branch point enzyme far from the major pathway of isoprenoids biosynthetic and a latent adjusting point, which manages carbon flux into triterpenes biosynthesis and sterols. The present study deals with the detailed characterization of SQS by bioinformatics approaches to evaluate physicochemical properties, structural characteristics including secondary and 3D structure prediction and functional analysis from eight plants related to Fabaceae family and Arabidopsis thaliana. Bioinformatics analysis revealed that SQS proteins have two transmembrane regions in the C-terminal. The predicted motifs were used to design universal degenerate primers for PCR analysis and other molecular applications. Phylogenetic analysis showed conserved regions at different stretches with maximum homology in amino acid residues within all SQSs. The secondary structure prediction results showed that the amino acid sequence of all squalene synthases had α helix and random coil as the main components. The reliability of the received model was confirmed using the ProSA and RAMPAGE programs. Determining of active site by CASTp proposes the possibility of using this protein as probable medication target. The findings of the present study may be useful for further assessments on characterization and cloning of squalene synthase.

show abstract

Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 77%

See 1 more Smart Citation

In silico analysis of squalene synthase in Fabaceae family using bioinformatics tools

Aminfar

Tohidfar

2018

Journal of Genetic Engineering and Biotechnology

View full text Add to dashboard Cite

show abstract

“…For segment A, Tyr (Y) 168 is presumably involved in the first step of catalysis, and the Asp-rich motif (DXXXD) of segment B is considered to be the active center for substrate binding with the presence of Mg 2+ . The two Phe (F) 283 and F 285 of segment C may contribute to the second-step catalysis [4,43]. Thirdly, the alpha helices of the monomeric SQS protein form a cave-like active center and transmembrane domain(s) at the C-terminus.…”

Section: Discussionmentioning

confidence: 99%

Molecular Cloning and Functional Identification of a Squalene Synthase Encoding Gene from Alfalfa (Medicago sativa L.)

Zhang

et al. 2019

IJMS

View full text Add to dashboard Cite

The quality of alfalfa, a main legume forage worldwide, is of great importance for the dairy industry and is affected by the content of triterpene saponins. These natural terpenoid products of triterpene aglycones are catalyzed by squalene synthase (SQS), a highly conserved enzyme present in eukaryotes. However, there is scare information on alfalfa SQS. Here, an open reading frame (ORF) of SQS was cloned from alfalfa. Sequence analysis showed MsSQS had the same exon/intron composition and shared high homology with its orthologs. Bioinformatic analysis revealed the deduced MsSQS had two transmembrane domains. When transiently expressed, GFP-MsSQS fusion protein was localized on the plasma membrane of onion epidermal cells. Removal of the C-terminal transmembrane domain of MsSQS improved solubility in Escherichia coli. MsSQS was preferably expressed in roots, followed by leaves and stems. MeJA treatment induced MsSQS expression and increased the content of total saponins. Overexpression of MsSQS in alfalfa led to the accumulation of total saponins, suggesting a correlation between MsSQS expression level with saponins content. Therefore, MsSQS is a canonical squalene synthase and contributes to saponin synthesis in alfalfa. This study provides a key candidate gene for genetic manipulation of the synthesis of triterpene saponins, which impact both plant and animal health.

show abstract

“…Motif Search tool identified two conserved motifs (16 residues long, 164YCHYVAGLVGHGLTQL179 and 28 residues long, 200MGLFLQKTNIIRDYYEDIREEPPRMFWP227) with the conserved signatory motif patterns of Y-[CSAM]-x(2)-[VSG]-A-[GSA]-[LIVAT]-[IV]-G-x(2)-[LMSC]-x(2)-[LIV] and [LIVM]-G-x(3)-Q-x(2,3)-[ND]-[IFL]-x-[RE]-D-[LIVMFY]-x(2)-[DE]-x(4,7)-R-x-[FY]-x-P. These conserved two motif sequences were previously reported in SQS derived from cucurbitaceae [ 63 ] and solanaceae [ 64 ] family plants with few residual substitutions.…”

Section: Resultsmentioning

confidence: 63%

Computational study to discover potent phytochemical inhibitors against drug target, squalene synthase from Leishmania donovani

Wadanambi¹,

Mannapperuma

2021

Heliyon

View full text Add to dashboard Cite

Aims The parasite, Leishmania donovani is responsible for lethal visceral leishmaniasis (VL) in humans. There is a need to investigate novel medicines as antileishmanial drugs, as medication currently introduced for leishmaniasis may cause resistance, serious side-effects, chemical instability and high cost. Therefore, this computational study was designed to explore potential phytochemical inhibitors against Leishmania donovani squalene synthase (LdSQS) enzyme, a drug target. Main methods Multiple sequence alignment was carried to detect conserved regions across squalene synthases from different Leishmania spp. Their evolutionary relationships were studied by generating phylogenetic tree. Homology modeling method was used to build a three dimensional model of the protein. The validated model was explored by docking simulation with the phytochemicals of interest to identify the most potent inhibitors. Two reported inhibitors were used as references in the virtual screening. The top hit compounds (binding energy less than -9 kcal/mol) were further subjected to intermolecular interaction analysis, pharmacophore modeling, pharmacokinetic and toxicity prediction. Key findings Seven phytochemicals displayed binding energies less than -9 kcal/mol hence demonstrating ability to be strongly bound to the active site of LdSQS to inhibit the enzymatic activity. Ancistrotanzanine B demonstrated the lowest binding affinity of -9.83 kcal/mol superior to reported inhibitors in literature. Conserved two aspartate rich regions and two signatory motifs were found in the L. donovani squalene synthase by multiple sequence alignment. In addition, study of pharmacophore modeling confirmed that top hit phytochemicals and the reported inhibitor (E5700) share common chemical features for their biochemical interaction with LdSQS. Among seven phytochemicals, 3-O-methyldiplacol showed admissible physicochemical, pharmacokinetic and toxicity predictions compared to the reported inhibitors. All seven phytochemicals satisfied in silico prediction criteria for oral bioavailability. Significance Based on the current study, these hits can be further structurally optimized and validated under laboratory conditions to develop antileishmanial drugs.

show abstract

In silico study of binding motifs in squalene synthase enzyme of secondary metabolic pathway solanaceae family

Cited by 6 publications

References 27 publications

In silico analysis of squalene synthase in Fabaceae family using bioinformatics tools

In silico analysis of squalene synthase in Fabaceae family using bioinformatics tools

Molecular Cloning and Functional Identification of a Squalene Synthase Encoding Gene from Alfalfa (Medicago sativa L.)

Computational study to discover potent phytochemical inhibitors against drug target, squalene synthase from Leishmania donovani

Contact Info

Product

Resources

About