Enzymatic deamination of the epigenetic base N-6-methyladenine

Siddhesh S. Kamat; Hao Fan; J. Michael Sauder; Stephen K. Burley; Brian K. Shoichet; Andrej Sali; Frank M. Raushel

doi:10.1021/ja110157u

Enzymatic deamination of the epigenetic base N-6-methyladenine

Siddhesh S. Kamat, Hao Fan, J. Michael Sauder, Stephen K. Burley, Brian K. Shoichet, Andrej Sali, Frank M. Raushel

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

Two enzymes of unknown function from the amidohydrolase superfamily were discovered to catalyze the deamination of N-6-methyladenine to hypoxanthine and methyl amine. The methylation of adenine in bacterial DNA is a common modification for the protection of host DNA against restriction endonucleases. The enzyme from Bacillus halodurans, Bh0637, catalyzes the deamination of N-6-methyladenine with a k_cat of 185 s^-1 and a k _cat/K_m of 2.5 x 10⁶ M^-1 s ^-1. Bh0637 catalyzes the deamination of N-6-methyladenine 2 orders of magnitude faster than adenine. A comparative model of Bh0637 was computed using the three-dimensional structure of Atu4426 (PDB code: 3NQB) as a structural template and computational docking was used to rationalize the preferential utilization of N-6-methyladenine over adenine. This is the first identification of an N-6-methyladenine deaminase (6-MAD).

Original language	English (US)
Pages (from-to)	2080-2083
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	133
Issue number	7
DOIs	https://doi.org/10.1021/ja110157u
State	Published - Feb 23 2011
Externally published	Yes

All Science Journal Classification (ASJC) codes

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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10.1021/ja110157u

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title = "Enzymatic deamination of the epigenetic base N-6-methyladenine",

abstract = "Two enzymes of unknown function from the amidohydrolase superfamily were discovered to catalyze the deamination of N-6-methyladenine to hypoxanthine and methyl amine. The methylation of adenine in bacterial DNA is a common modification for the protection of host DNA against restriction endonucleases. The enzyme from Bacillus halodurans, Bh0637, catalyzes the deamination of N-6-methyladenine with a kcat of 185 s-1 and a k cat/Km of 2.5 x 106 M-1 s -1. Bh0637 catalyzes the deamination of N-6-methyladenine 2 orders of magnitude faster than adenine. A comparative model of Bh0637 was computed using the three-dimensional structure of Atu4426 (PDB code: 3NQB) as a structural template and computational docking was used to rationalize the preferential utilization of N-6-methyladenine over adenine. This is the first identification of an N-6-methyladenine deaminase (6-MAD).",

author = "Kamat, {Siddhesh S.} and Hao Fan and Sauder, {J. Michael} and Burley, {Stephen K.} and Shoichet, {Brian K.} and Andrej Sali and Raushel, {Frank M.}",

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doi = "10.1021/ja110157u",

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AU - Kamat, Siddhesh S.

AU - Fan, Hao

AU - Sauder, J. Michael

AU - Burley, Stephen K.

AU - Shoichet, Brian K.

AU - Sali, Andrej

AU - Raushel, Frank M.

PY - 2011/2/23

Y1 - 2011/2/23

N2 - Two enzymes of unknown function from the amidohydrolase superfamily were discovered to catalyze the deamination of N-6-methyladenine to hypoxanthine and methyl amine. The methylation of adenine in bacterial DNA is a common modification for the protection of host DNA against restriction endonucleases. The enzyme from Bacillus halodurans, Bh0637, catalyzes the deamination of N-6-methyladenine with a kcat of 185 s-1 and a k cat/Km of 2.5 x 106 M-1 s -1. Bh0637 catalyzes the deamination of N-6-methyladenine 2 orders of magnitude faster than adenine. A comparative model of Bh0637 was computed using the three-dimensional structure of Atu4426 (PDB code: 3NQB) as a structural template and computational docking was used to rationalize the preferential utilization of N-6-methyladenine over adenine. This is the first identification of an N-6-methyladenine deaminase (6-MAD).

AB - Two enzymes of unknown function from the amidohydrolase superfamily were discovered to catalyze the deamination of N-6-methyladenine to hypoxanthine and methyl amine. The methylation of adenine in bacterial DNA is a common modification for the protection of host DNA against restriction endonucleases. The enzyme from Bacillus halodurans, Bh0637, catalyzes the deamination of N-6-methyladenine with a kcat of 185 s-1 and a k cat/Km of 2.5 x 106 M-1 s -1. Bh0637 catalyzes the deamination of N-6-methyladenine 2 orders of magnitude faster than adenine. A comparative model of Bh0637 was computed using the three-dimensional structure of Atu4426 (PDB code: 3NQB) as a structural template and computational docking was used to rationalize the preferential utilization of N-6-methyladenine over adenine. This is the first identification of an N-6-methyladenine deaminase (6-MAD).

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JO - Journal of the American Chemical Society

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Enzymatic deamination of the epigenetic base N-6-methyladenine

Abstract

All Science Journal Classification (ASJC) codes

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