MODELING AND MOLECULAR DOCKING STUDIES ON &lt;i&gt;ASPERGILLUS&lt;/i&gt; RNASE &lt;i&gt;NIGER&lt;/i&gt; AND &lt;i&gt;LEISHMANIA DONOVANI&lt;/i&gt; ACTIN: ANTILEISHMANIAL ACTIVITY

Gundampati,

doi:10.3844/ajbbsp.2013.318.328

Cited by 10 publications

(5 citation statements)

References 34 publications

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“…However, recent elucidation of Gtf crystal structure combined with 3D modelling revealed several additional binding motifs [56–59]. Moreover, the Gtf protein-ligand mechanisms are rather complex, involving intricate conformational changes (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Based on protein chemistry and biochemical analyses, a series of repeat motifs of amino acids found at the carboxy terminus of Gtfs (glucan-binding domain) could recognize and bind to glucose moieties [ 22 , 55 ]. However, recent elucidation of Gtf crystal structure combined with 3D modelling revealed several additional binding motifs [ 56 – 59 ]. Moreover, the Gtf protein-ligand mechanisms are rather complex, involving intricate conformational changes (e.g.…”

Section: Discussionmentioning

confidence: 99%

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Candida albicans mannans mediate Streptococcus mutans exoenzyme GtfB binding to modulate cross-kingdom biofilm development in vivo

et al. 2017

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Candida albicans is frequently detected with heavy infection by Streptococcus mutans in plaque-biofilms from children with early-childhood caries (ECC). This cross-kingdom biofilm contains an extensive matrix of extracellular α-glucans that is produced by an exoenzyme (GtfB) secreted by S. mutans. Here, we report that mannans located on the outer surface of C. albicans cell-wall mediates GtfB binding, enhancing glucan-matrix production and modulating bacterial-fungal association within biofilms formed in vivo. Using single-molecule atomic force microscopy, we determined that GtfB binds with remarkable affinity to mannans and to the C. albicans surface, forming a highly stable and strong bond (1–2 nN). However, GtfB binding properties to C. albicans was compromised in strains defective in O-mannan (pmt4ΔΔ) or N-mannan outer chain (och1ΔΔ). In particular, the binding strength of GtfB on och1ΔΔ strain was severely disrupted (>3-fold reduction vs. parental strain). In turn, the GtfB amount on the fungal surface was significantly reduced, and the ability of C. albicans mutant strains to develop mixed-species biofilms with S. mutans was impaired. This phenotype was independent of hyphae or established fungal-biofilm regulators (EFG1, BCR1). Notably, the mechanical stability of the defective biofilms was weakened, resulting in near complete biomass removal by shear forces. In addition, these in vitro findings were confirmed in vivo using a rodent biofilm model. Specifically, we observed that C. albicans och1ΔΔ was unable to form cross-kingdom biofilms on the tooth surface of rats co-infected with S. mutans. Likewise, co-infection with S. mutans defective in GtfB was also incapable of forming mixed-species biofilms. Taken together, the data support a mechanism whereby S. mutans-secreted GtfB binds to the mannan layer of C. albicans to promote extracellular matrix formation and their co-existence within biofilms. Enhanced understanding of GtfB-Candida interactions may provide new perspectives for devising effective therapies to disrupt this cross-kingdom relationship associated with an important childhood oral disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Candida albicans mannans mediate Streptococcus mutans exoenzyme GtfB binding to modulate cross-kingdom biofilm development in vivo

et al. 2017

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“…Therefore, docking of αMG on Gtf was carried out to explore if/how this compound might interact with the enzymes. In our study, when the GtfC enzyme was docked with αMG, the energy value obtained by HEX software was −511.36 Kcal/mol, indicating a stable and strong binding between the two molecules [55] . The best docked structure, visualized by UCSF Chimera molecular modeling system version 1.8 ( http://www.cgl.ucsf.edu/chimera/download.html ), showed the interaction of four amino acids (Trp 517, Glu 515, Asp 588 and Asn 481) ( Figure 5A and 5B ).…”

Section: Resultsmentioning

confidence: 58%

“…Docking studies support the prediction of conformation and binding affinity for selected molecules against a given target protein [55] . Therefore, docking of αMG on Gtf was carried out to explore if/how this compound might interact with the enzymes.…”

Section: Resultsmentioning

confidence: 92%

α-Mangostin Disrupts the Development of Streptococcus mutans Biofilms and Facilitates Its Mechanical Removal

et al. 2014

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α-Mangostin (αMG) has been reported to be an effective antimicrobial agent against planktonic cells of Streptococcus mutans, a biofilm-forming and acid-producing cariogenic organism. However, its anti-biofilm activity remains to be determined. We examined whether αMG, a xanthone purified from Garcinia mangostana L grown in Vietnam, disrupts the development, acidogenicity, and/or the mechanical stability of S. mutans biofilms. Treatment regimens simulating those experienced clinically (twice-daily, 60 s exposure each) were used to assess the bioactivity of αMG using a saliva-coated hydroxyapatite (sHA) biofilm model. Topical applications of early-formed biofilms with αMG (150 µM) effectively reduced further biomass accumulation and disrupted the 3D architecture of S. mutans biofilms. Biofilms treated with αMG had lower amounts of extracellular insoluble and intracellular iodophilic polysaccharides (30–45%) than those treated with vehicle control (P<0.05), while the number of viable bacterial counts was unaffected. Furthermore, αMG treatments significantly compromised the mechanical stability of the biofilm, facilitating its removal from the sHA surface when subjected to a constant shear stress of 0.809 N/m2 (>3-fold biofilm detachment from sHA vs. vehicle-treated biofilms; P<0.05). Moreover, acid production by S. mutans biofilms was disrupted following αMG treatments (vs. vehicle-control, P<0.05). The activity of enzymes associated with glucan synthesis, acid production, and acid tolerance (glucosyltransferases B and C, phosphotransferase-PTS system, and F1F0-ATPase) were significantly inhibited by αMG. The expression of manL, encoding a key component of the mannose PTS, and gtfB were slightly repressed by αMG treatment (P<0.05), while the expression of atpD (encoding F-ATPase) and gtfC genes was unaffected. Hence, this study reveals that brief exposures to αMG can disrupt the development and structural integrity of S. mutans biofilms, at least in part via inhibition of key enzymatic systems associated with exopolysaccharide synthesis and acidogenicity. αMG could be an effective anti-virulence additive for the control and/or removal of cariogenic biofilms.

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“…Thus, 450 K simulation represents the start of unfolding process and 550 K simulation represents the unfolded state. We compare the physical parameter (RMSD, SASA and Rg) of wild type and mutants to represent the thermostability of both molecules (Gundampati et al, 2013). Significant increase in Solvent Accessible Surface Area (SASA) will happen when a protein molecule starts to lose its stabilizing interactions (intermolecular hydrogen bond, electrostatic and van der Waals interaction) and hydrophobic core of protein molecule starts to collapse; thus the protein will be more readily accessible to the solvent molecule (Day et al, 2002;Yan et al, 2010).…”

Section: Molecular Dynamics Simulation Of Mutantsmentioning

confidence: 99%

DESIGN OF <i>CANDIDA ANTARCTICA</i> LIPASE B THERMOSTABILITY IMPROVEMENT BY INTRODUCING EXTRA DISULFIDE BOND INTO THE ENZYME

Tambunan¹

2014

OnLine Journal of Biological Sciences

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Candida Antarctica Lipase B (CALB) is extensively studied in enzymatic production of biodiesel, pharmaceutical products, detergents and other chemicals. One drawback of using CALB is its relatively low optimum temperature at 313 K (40°C). The objective of this research is to design CALB mutant with improved thermostability by introducing extra disulfide bond. Molecular dynamic simulation was conducted to get better insight into the process of thermal denaturation or unfolding in CALB. Thermal denaturation of CALB was accelerated by conducting simulation at high temperature. Molecular dynamic simulation of CALB was performed with GROMACS software package at 300-700 K. Prediction of possible mutation was done using "Disulfide by Design TM " software. Selection of mutated residues was based on flexibility analysis of CALB. From those analyses, three mutants were designed, which are Mutant-1 (73LeuCys/151AlaCys), Mutant-2 (155TrpCys/294GluCys) and Mutant-3 (43ThrCys/67SerCys). Parameters that were used to compare the thermostability of mutant with wild type enzyme were Root Mean Square Deviations (RMSD), Solvent Accessible Surface Area (SASA), Radius of gyration (Rg) and secondary structure. Molecular dynamic simulation conducted on those three mutants showed that Mutant-1 has better thermostability compared to wild type CALB. We proposed the order of mutant thermostability improvement as follows: Mutant-1, Mutant-2 and Mutant-3, with Mutant-1 having better potential thermostability improvement and Mutant-3, the least stable.

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MODELING AND MOLECULAR DOCKING STUDIES ON <i>ASPERGILLUS</i> RNASE <i>NIGER</i> AND <i>LEISHMANIA DONOVANI</i> ACTIN: ANTILEISHMANIAL ACTIVITY

Cited by 10 publications

References 34 publications

Candida albicans mannans mediate Streptococcus mutans exoenzyme GtfB binding to modulate cross-kingdom biofilm development in vivo

Candida albicans mannans mediate Streptococcus mutans exoenzyme GtfB binding to modulate cross-kingdom biofilm development in vivo

α-Mangostin Disrupts the Development of Streptococcus mutans Biofilms and Facilitates Its Mechanical Removal

DESIGN OF <i>CANDIDA ANTARCTICA</i> LIPASE B THERMOSTABILITY IMPROVEMENT BY INTRODUCING EXTRA DISULFIDE BOND INTO THE ENZYME

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