New Insight into the Substrate Selectivity of Bovine Milk γ-glutamyl Transferase via Structural and Molecular Dynamics Predictions

Research output: Contribution to journal › Journal article › Research › peer-review

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New Insight into the Substrate Selectivity of Bovine Milk γ-glutamyl Transferase via Structural and Molecular Dynamics Predictions. / Cao, Lichuang; Hunt, Cameron J.; Meyer, Anne S.; Lametsch, René.

In: Molecules, Vol. 28, No. 12, 4657, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Cao, L, Hunt, CJ, Meyer, AS & Lametsch, R 2023, 'New Insight into the Substrate Selectivity of Bovine Milk γ-glutamyl Transferase via Structural and Molecular Dynamics Predictions', Molecules, vol. 28, no. 12, 4657. https://doi.org/10.3390/molecules28124657

APA

Cao, L., Hunt, C. J., Meyer, A. S., & Lametsch, R. (2023). New Insight into the Substrate Selectivity of Bovine Milk γ-glutamyl Transferase via Structural and Molecular Dynamics Predictions. Molecules, 28(12), [4657]. https://doi.org/10.3390/molecules28124657

Vancouver

Cao L, Hunt CJ, Meyer AS, Lametsch R. New Insight into the Substrate Selectivity of Bovine Milk γ-glutamyl Transferase via Structural and Molecular Dynamics Predictions. Molecules. 2023;28(12). 4657. https://doi.org/10.3390/molecules28124657

Author

Cao, Lichuang ; Hunt, Cameron J. ; Meyer, Anne S. ; Lametsch, René. / New Insight into the Substrate Selectivity of Bovine Milk γ-glutamyl Transferase via Structural and Molecular Dynamics Predictions. In: Molecules. 2023 ; Vol. 28, No. 12.

Bibtex

@article{73ecd9454c1449f0a73ee9bfbc3d2a3b,
title = "New Insight into the Substrate Selectivity of Bovine Milk γ-glutamyl Transferase via Structural and Molecular Dynamics Predictions",
abstract = "Bovine milk γ-glutamyltransferase (BoGGT) can produce γ-glutamyl peptides using L-glutamine as a donor substrate, and the transpeptidase activity is highly dependent on both γ-glutamyl donors and acceptors. To explore the molecular mechanism behind the donor and acceptor substrate preferences for BoGGT, molecular docking and molecular dynamic simulations were performed with L-glutamine and L-γ-glutamyl-p-nitroanilide (γ-GpNA) as donors. Ser450 is a crucial residue for the interactions between BoGGT and donors. BoGGT forms more hydrogen bonds with L-glutamine than γ-GpNA, promoting the binding affinity between BoGGT and L-glutamine. Gly379, Ile399, and Asn400 are crucial residues for the interactions between the BoGGT intermediate and acceptors. The BoGGT intermediate forms more hydrogen bonds with Val-Gly than L-methionine and L-leucine, which can promote the transfer of the γ-glutamyl group from the intermediate to Val-Gly. This study reveals the critical residues responsible for the interactions of donors and acceptors with the BoGGT and provides a new understanding of the substrate selectivity and catalytic mechanism of GGT.",
keywords = "molecular docking, molecular dynamic simulation, γ-glutamyl acceptor, γ-glutamyl donor, γ-glutamyl-enzyme intermediate",
author = "Lichuang Cao and Hunt, {Cameron J.} and Meyer, {Anne S.} and Ren{\'e} Lametsch",
note = "Publisher Copyright: {\textcopyright} 2023 by the authors.",
year = "2023",
doi = "10.3390/molecules28124657",
language = "English",
volume = "28",
journal = "Molecules",
issn = "1420-3049",
publisher = "M D P I AG",
number = "12",

}

RIS

TY - JOUR

T1 - New Insight into the Substrate Selectivity of Bovine Milk γ-glutamyl Transferase via Structural and Molecular Dynamics Predictions

AU - Cao, Lichuang

AU - Hunt, Cameron J.

AU - Meyer, Anne S.

AU - Lametsch, René

N1 - Publisher Copyright: © 2023 by the authors.

PY - 2023

Y1 - 2023

N2 - Bovine milk γ-glutamyltransferase (BoGGT) can produce γ-glutamyl peptides using L-glutamine as a donor substrate, and the transpeptidase activity is highly dependent on both γ-glutamyl donors and acceptors. To explore the molecular mechanism behind the donor and acceptor substrate preferences for BoGGT, molecular docking and molecular dynamic simulations were performed with L-glutamine and L-γ-glutamyl-p-nitroanilide (γ-GpNA) as donors. Ser450 is a crucial residue for the interactions between BoGGT and donors. BoGGT forms more hydrogen bonds with L-glutamine than γ-GpNA, promoting the binding affinity between BoGGT and L-glutamine. Gly379, Ile399, and Asn400 are crucial residues for the interactions between the BoGGT intermediate and acceptors. The BoGGT intermediate forms more hydrogen bonds with Val-Gly than L-methionine and L-leucine, which can promote the transfer of the γ-glutamyl group from the intermediate to Val-Gly. This study reveals the critical residues responsible for the interactions of donors and acceptors with the BoGGT and provides a new understanding of the substrate selectivity and catalytic mechanism of GGT.

AB - Bovine milk γ-glutamyltransferase (BoGGT) can produce γ-glutamyl peptides using L-glutamine as a donor substrate, and the transpeptidase activity is highly dependent on both γ-glutamyl donors and acceptors. To explore the molecular mechanism behind the donor and acceptor substrate preferences for BoGGT, molecular docking and molecular dynamic simulations were performed with L-glutamine and L-γ-glutamyl-p-nitroanilide (γ-GpNA) as donors. Ser450 is a crucial residue for the interactions between BoGGT and donors. BoGGT forms more hydrogen bonds with L-glutamine than γ-GpNA, promoting the binding affinity between BoGGT and L-glutamine. Gly379, Ile399, and Asn400 are crucial residues for the interactions between the BoGGT intermediate and acceptors. The BoGGT intermediate forms more hydrogen bonds with Val-Gly than L-methionine and L-leucine, which can promote the transfer of the γ-glutamyl group from the intermediate to Val-Gly. This study reveals the critical residues responsible for the interactions of donors and acceptors with the BoGGT and provides a new understanding of the substrate selectivity and catalytic mechanism of GGT.

KW - molecular docking

KW - molecular dynamic simulation

KW - γ-glutamyl acceptor

KW - γ-glutamyl donor

KW - γ-glutamyl-enzyme intermediate

U2 - 10.3390/molecules28124657

DO - 10.3390/molecules28124657

M3 - Journal article

C2 - 37375212

AN - SCOPUS:85163877050

VL - 28

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 12

M1 - 4657

ER -

ID: 361849069