The role of conserved arginine in the GH70 family

A computational study of the structural features and their implications on the catalytic mechanism of GTF-SI from: Streptoccocus mutans

Leslie Sánchez, Fernanda Mendoza, Joel B. Alderete, Verónica A. Jiménez, Gonzalo A. Jaña

Resultado de la investigación: Article

Resumen

In this work, molecular dynamics and QM/MM calculations were employed to examine the structural and catalytic features of the retaining glucosyltransferase GTF-SI from the GH70 family, which participates in the process of caries formation. Our goal was to obtain a deeper understanding of the role of R475 in the mechanism of sucrose breakage. This residue is highly conserved in the GH70 family and so far there has been no evidence that shows what could be the role of this residue in the catalysis performed by GTF-SI. In order to understand the structural role of R475 in the native enzyme, we built full enzyme models of the wild type and the mutants R475A and R475Q. These models were addressed by means of molecular dynamics simulations, which allowed the assessment of the dynamical effect of the R475 mutation on the active site. Then, representative structures were chosen for each one of the mutant models and QM/MM calculations were carried out to unravel the catalytic role of R475. Our results show that the R475 mutation increases the flexibility of the enzyme, which triggers the entrance of water molecules in the active site. In addition, QM/MM calculations indicate that R475 is able to provide a great stabilization to the carboxylate moiety of the acid/base E515, which is an essential characteristic favoring the proton transfer process that promotes the glycosidic bond breakage of sucrose.

Idioma originalEnglish
Páginas (desde-hasta)6269-6276
Número de páginas8
PublicaciónOrganic and Biomolecular Chemistry
Volumen17
N.º25
DOI
EstadoPublished - 7 jul 2019

Huella dactilar

International System of Units
Arginine
enzymes
sucrose
Molecular Dynamics Simulation
mutations
Sucrose
Molecular dynamics
Catalytic Domain
Enzymes
molecular dynamics
Glucosyltransferases
Mutation
Proton transfer
retaining
Catalysis
entrances
carboxylates
catalysis
Protons

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Citar esto

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title = "The role of conserved arginine in the GH70 family: A computational study of the structural features and their implications on the catalytic mechanism of GTF-SI from: Streptoccocus mutans",
abstract = "In this work, molecular dynamics and QM/MM calculations were employed to examine the structural and catalytic features of the retaining glucosyltransferase GTF-SI from the GH70 family, which participates in the process of caries formation. Our goal was to obtain a deeper understanding of the role of R475 in the mechanism of sucrose breakage. This residue is highly conserved in the GH70 family and so far there has been no evidence that shows what could be the role of this residue in the catalysis performed by GTF-SI. In order to understand the structural role of R475 in the native enzyme, we built full enzyme models of the wild type and the mutants R475A and R475Q. These models were addressed by means of molecular dynamics simulations, which allowed the assessment of the dynamical effect of the R475 mutation on the active site. Then, representative structures were chosen for each one of the mutant models and QM/MM calculations were carried out to unravel the catalytic role of R475. Our results show that the R475 mutation increases the flexibility of the enzyme, which triggers the entrance of water molecules in the active site. In addition, QM/MM calculations indicate that R475 is able to provide a great stabilization to the carboxylate moiety of the acid/base E515, which is an essential characteristic favoring the proton transfer process that promotes the glycosidic bond breakage of sucrose.",
author = "Leslie S{\'a}nchez and Fernanda Mendoza and Alderete, {Joel B.} and Jim{\'e}nez, {Ver{\'o}nica A.} and Ja{\~n}a, {Gonzalo A.}",
year = "2019",
month = "7",
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doi = "10.1039/c9ob01055f",
language = "English",
volume = "17",
pages = "6269--6276",
journal = "Organic and Biomolecular Chemistry",
issn = "1477-0520",
publisher = "Royal Society of Chemistry",
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TY - JOUR

T1 - The role of conserved arginine in the GH70 family

T2 - A computational study of the structural features and their implications on the catalytic mechanism of GTF-SI from: Streptoccocus mutans

AU - Sánchez, Leslie

AU - Mendoza, Fernanda

AU - Alderete, Joel B.

AU - Jiménez, Verónica A.

AU - Jaña, Gonzalo A.

PY - 2019/7/7

Y1 - 2019/7/7

N2 - In this work, molecular dynamics and QM/MM calculations were employed to examine the structural and catalytic features of the retaining glucosyltransferase GTF-SI from the GH70 family, which participates in the process of caries formation. Our goal was to obtain a deeper understanding of the role of R475 in the mechanism of sucrose breakage. This residue is highly conserved in the GH70 family and so far there has been no evidence that shows what could be the role of this residue in the catalysis performed by GTF-SI. In order to understand the structural role of R475 in the native enzyme, we built full enzyme models of the wild type and the mutants R475A and R475Q. These models were addressed by means of molecular dynamics simulations, which allowed the assessment of the dynamical effect of the R475 mutation on the active site. Then, representative structures were chosen for each one of the mutant models and QM/MM calculations were carried out to unravel the catalytic role of R475. Our results show that the R475 mutation increases the flexibility of the enzyme, which triggers the entrance of water molecules in the active site. In addition, QM/MM calculations indicate that R475 is able to provide a great stabilization to the carboxylate moiety of the acid/base E515, which is an essential characteristic favoring the proton transfer process that promotes the glycosidic bond breakage of sucrose.

AB - In this work, molecular dynamics and QM/MM calculations were employed to examine the structural and catalytic features of the retaining glucosyltransferase GTF-SI from the GH70 family, which participates in the process of caries formation. Our goal was to obtain a deeper understanding of the role of R475 in the mechanism of sucrose breakage. This residue is highly conserved in the GH70 family and so far there has been no evidence that shows what could be the role of this residue in the catalysis performed by GTF-SI. In order to understand the structural role of R475 in the native enzyme, we built full enzyme models of the wild type and the mutants R475A and R475Q. These models were addressed by means of molecular dynamics simulations, which allowed the assessment of the dynamical effect of the R475 mutation on the active site. Then, representative structures were chosen for each one of the mutant models and QM/MM calculations were carried out to unravel the catalytic role of R475. Our results show that the R475 mutation increases the flexibility of the enzyme, which triggers the entrance of water molecules in the active site. In addition, QM/MM calculations indicate that R475 is able to provide a great stabilization to the carboxylate moiety of the acid/base E515, which is an essential characteristic favoring the proton transfer process that promotes the glycosidic bond breakage of sucrose.

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U2 - 10.1039/c9ob01055f

DO - 10.1039/c9ob01055f

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