Using the Amino Acid Network to Modulate the Hydrolytic Activity of β-Glycosidases

Tamaki, Fábio K.; Souza, Diorge P.; Souza, Valquiria P.; Ikegami, Cecília M.; Farah, Chuck S.; Marana, Sandro R.

doi:10.1371/journal.pone.0167978

Cited by 18 publications

(27 citation statements)

References 49 publications

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“…13 On the other hand, different β-glucosidases showed catalytic activity within or outside of the active site for enzymatic activity, which is still unclear to the researcher. 20 In the present computational prediction highest binding energy was obtained for Bicyclogermacrene volatile oil found in leaves of T. errecta. It is well-known that inhibition of βglucosidase activity of fungus prevent fungal pathogenicity in host plants.…”

Section: Resultsmentioning

confidence: 58%

In silico approach of receptor-ligand binding and interaction: Established phytoligands from Tagetes errecta Linn. against bacterial β-glucosidase receptor

Lahiri

Talukdar

Talapatra³

2019

J. Drug Delivery Ther.

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The medicinal plant, Tagetes errecta Linn. is a common ornamental plant and leaves of this plant are containing phytochemicals (volatile oil) that inhibit the growth of bacteria, fungi and known natural antimicrobial agents. The objective of the present study was to detect receptor-ligand binding energy and interaction through molecular docking for phytoligands established in the leaves of T. errecta against β-glucosidase receptor (PDB ID: 3AHZ). Molecular docking was performed by using PyRx (Version 0.8) for the structure-based virtual screening and visualized the interaction in the molecular graphic laboratory (MGL) tool (Version 1.5.6). Among 25 phytochemicals and 2 synthetic compounds (Carbendazim and 2-Amino-2-hydroxymethyl-propane-1,3-diol), binding energy value was obtained highest in Bicyclogermacrene (-6.4 Kcal/mol) and lowest in Octanol (-4.4 Kcal/mol) and Carbendazim and 2-Amino-2-hydroxymethyl-propane-1,3-diol showed -6.7 Kcal/mol and -3.5 Kcal/mol all of these showed no hydrogen bonding. The binding interaction of target protein with this phytocompound found binding at the mouth of the active site may be treated as competitive inhibitor. In conclusion, phytocompound Bicyclogermacrene can be alternative of synthetic fungicide as per binding energy value and interaction. It is suggesting further pharmacological and toxicological assay with this phytocompound after isolation from ornamental plant (T. errecta).

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Section: Resultsmentioning

confidence: 58%

In silico approach of receptor-ligand binding and interaction: Established phytoligands from Tagetes errecta Linn. against bacterial β-glucosidase receptor

Lahiri

Talukdar

Talapatra³

2019

J. Drug Delivery Ther.

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“…The glycone binding regions in the active site pocket of β-glucosidase are typically well-conserved [37-39], as can be seen in Fig. 3a, Trp122 in the glycone binding region is conserved across most of the glucose tolerant β-glucosidase except in O08324 (the enzyme retains 100 % specific activity up to 4 M Glc) wherein a Phe is located at the equivalent position [15].…”

Section: Resultsmentioning

confidence: 99%

Elucidating the regulation of glucose tolerance through the interaction between the reaction product and active site pocket residues of a β-glucosidase from Halothermothrix orenii

Sinha

Das

Konar

et al. 2019

Preprint

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2 β-glucosidase catalyzes the hydrolysis of β-1,4 linkage between two glucose molecules in cello-3 oligosaccharides and is prone to inhibition by the reaction product glucose. Relieving the glucose inhibition 4 of β-glucosidase is a significant challenge. Towards the goal of understanding how glucose interacts with 5 β-glucosidase, we expressed in Escherichia coli, the Hore_15280 gene encoding a β-glucosidase in 6 Halothermothrix orenii. Our results show that the enzyme is glucose tolerant, and its activity stimulated in 7 the presence of up to 0.5 M glucose. NMR analyses show the unexpected interactions between glucose and 8 the β-glucosidase at lower concentrations of glucose that however does not lead to enzyme inhibition. We 9 identified non-conserved residues at the aglycone-binding and the gatekeeper site and show that increased 10 hydrophobicity at the pocket entrance and a reduction in steric hindrances are critical towards enhanced 11 substrate accessibility and significant improvement in activity. Analysis of structures and in combination 12 with molecular dynamics simulations show that glucose increases the accessibility of the substrate by 13 enhancing the structural flexibility of the active site pocket and may explain the stimulation in specific 14 activity up to 0.5 M glucose. Such novel regulation of β-glucosidase activity by its reaction product may 15 offer novel ways of engineering glucose tolerance.

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“…transglicosilação" das beta-glicosidases, como a produção de oligossacarídeos e alquilglicosídeos a partir de açucares mais simples (Singhania et al, 2016). (Marana et al, 2001;Marana et al, 2003;Tamaki et al, 2016).…”

Section: N D Equação 13unclassified

“…O sítio ativo de beta-glicosidases é dividido em subsítios, que são regiões com tamanho suficiente para ligar uma unidade monossacarídica, conforme representado na figura 33 (Marana, 2006 (Marana et al, 2001;Marana, 2006;Tamaki et al, 2016).…”

Section: N D Equação 13unclassified

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Papel das redes estruturais proteicas nas propriedades de uma beta-glicosidase

Souza¹

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Analysis of protein structures as networks has been shown a powerful tool to understand their properties and to identify important residues. In the network analysis, residues that interact with each other are called connected. Some residues are essential to shorten the connection pathways between distant residues in the protein structure, being called central. Central residues have been proposed to have important roles in catalysis, thermal stability and allostery. In order to experimentally assess the correlation between the residue centrality and its importance in the protein properties, we use two approaches (chapter 1): The first one is to make single mutations at the central residues of a betaglucosidase Sfβgly, changing those residues to alanine. The second one is to perturb a central residue (F251) by changing its environment through single mutations that introduces voids or additional volume. Next, we evaluate how those mutations affect the protein thermostability and function. In general, we have observed (chapter 2) that mutations at central residues reduce the Tm in 2-15°C and increase the unfolding rate up to 20 times, suggesting that damages in the central residues make the protein more unstable. Moreover, we have observed (chapter 3) that the perturbation of the central residues reduces Sfβgly catalysis, which seems to arise from the same cause that lead to the loss of thermal stability. Besides that, in chapter 4, the investigation of oligomeric state of Sfβgli using SAXS indicated that this protein is mainly a dimer in 100 mM citrate-phosphate pH 6,0, whereas it forms large oligomers, possibly dodecamers, in 10 mM phosphate pH 6,0. In parallel it was shown that Sfβgly undergoes an activation process in 10 mM phosphate and its kinetic parameters converge to those observed for Sfβgly in 100 mM citrate-phosphate. Protein Structural Networks were built considering also that there are links between the polypeptidic chains of the Sfβgly oligomers. We observed 5 residues that are central in all kind of oligomeric structures here analyzed. Three of these residues, E187, P188 and N329, play important roles in the catalysis of this enzyme, and two of them (S247 and N249 are described in this thesis. Lastly, in the chapter 5, we observed that central residues by closeness, betweeness and C ΔLp are concentrated at the top of the beta-barrel (C-terminal end of the beta-strands and subsequent loops), suggesting that this region, where the active site is placed, is close, in terms of contacts, to the whole Sfβgly structure. Moreover, we have built the Protein Structural Network of 21 beta-glucosidases of the Glucoside Hydrolases family 1, revealing that the closeness central residues are highly conserved, being located in the active site of these enzymes. On the other hand, betweeness central residues are located in the same sites in the structure of different beta-glucosidases, but they are not always conserved. Shortly, these data experimentally support the hypothesis that the residue centrality in Protein Str...

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Using the Amino Acid Network to Modulate the Hydrolytic Activity of β-Glycosidases

Cited by 18 publications

References 49 publications

In silico approach of receptor-ligand binding and interaction: Established phytoligands from Tagetes errecta Linn. against bacterial β-glucosidase receptor

In silico approach of receptor-ligand binding and interaction: Established phytoligands from Tagetes errecta Linn. against bacterial β-glucosidase receptor

Elucidating the regulation of glucose tolerance through the interaction between the reaction product and active site pocket residues of a β-glucosidase from Halothermothrix orenii

Papel das redes estruturais proteicas nas propriedades de uma beta-glicosidase

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