Insights into enzyme evolution revealed by the structure of methylaspartate ammonia lyase

C. W. Levy; P. A. Buckley; S. Sedelnikova; Y. Kato; Y. Asano; D. W. Rice; P. J. Baker

doi:10.1016/S0969-2126(01)00696-7

Insights into enzyme evolution revealed by the structure of methylaspartate ammonia lyase

C. W. Levy, P. A. Buckley, S. Sedelnikova, Y. Kato, Y. Asano, D. W. Rice, P. J. Baker

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

Abstract

Methylaspartate ammonia lyase (MAL) catalyzes the magnesium-dependent reversible α,β-elimination of ammonia from L-threo-(2S,3S)-3-methylaspartic acid to mesaconic acid. The 1.3 Å MAD crystal structure of the dimeric Citrobacter amalonaticus MAL shows that each subunit comprises two domains, one of which adopts the classical TIM barrel fold, with the active site at the C-terminal end of the barrel. Despite very low sequence similarity, the structure of MAL is closely related to those of representative members of the enolase superfamily, indicating that the mechanism of MAL involves the initial abstraction of a proton α to the 3-carboxyl of (2S,3S)-3-methylasparic acid to yield an enolic intermediate. This analysis resolves the conflict that had linked MAL to the histidine and phenylalanine ammonia lyase family of enzymes.

Original language	English
Pages (from-to)	105-113
Number of pages	9
Journal	Structure
Volume	10
Issue number	1
DOIs	https://doi.org/10.1016/S0969-2126(01)00696-7
Publication status	Published - Jan 2002

Keywords

Enolase superfamily
Evolution
MAD phasing
Methylaspartate ammonia lyase
Selenomethionine
X-ray crystallography

Research Beacons, Institutes and Platforms

Manchester Institute of Biotechnology

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10.1016/S0969-2126(01)00696-7

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title = "Insights into enzyme evolution revealed by the structure of methylaspartate ammonia lyase",

abstract = "Methylaspartate ammonia lyase (MAL) catalyzes the magnesium-dependent reversible α,β-elimination of ammonia from L-threo-(2S,3S)-3-methylaspartic acid to mesaconic acid. The 1.3 {\AA} MAD crystal structure of the dimeric Citrobacter amalonaticus MAL shows that each subunit comprises two domains, one of which adopts the classical TIM barrel fold, with the active site at the C-terminal end of the barrel. Despite very low sequence similarity, the structure of MAL is closely related to those of representative members of the enolase superfamily, indicating that the mechanism of MAL involves the initial abstraction of a proton α to the 3-carboxyl of (2S,3S)-3-methylasparic acid to yield an enolic intermediate. This analysis resolves the conflict that had linked MAL to the histidine and phenylalanine ammonia lyase family of enzymes.",

keywords = "Enolase superfamily, Evolution, MAD phasing, Methylaspartate ammonia lyase, Selenomethionine, X-ray crystallography",

author = "Levy, {C. W.} and Buckley, {P. A.} and S. Sedelnikova and Y. Kato and Y. Asano and Rice, {D. W.} and Baker, {P. J.}",

year = "2002",

month = jan,

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journal = "Structure",

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T1 - Insights into enzyme evolution revealed by the structure of methylaspartate ammonia lyase

AU - Levy, C. W.

AU - Buckley, P. A.

AU - Sedelnikova, S.

AU - Kato, Y.

AU - Asano, Y.

AU - Rice, D. W.

AU - Baker, P. J.

PY - 2002/1

Y1 - 2002/1

N2 - Methylaspartate ammonia lyase (MAL) catalyzes the magnesium-dependent reversible α,β-elimination of ammonia from L-threo-(2S,3S)-3-methylaspartic acid to mesaconic acid. The 1.3 Å MAD crystal structure of the dimeric Citrobacter amalonaticus MAL shows that each subunit comprises two domains, one of which adopts the classical TIM barrel fold, with the active site at the C-terminal end of the barrel. Despite very low sequence similarity, the structure of MAL is closely related to those of representative members of the enolase superfamily, indicating that the mechanism of MAL involves the initial abstraction of a proton α to the 3-carboxyl of (2S,3S)-3-methylasparic acid to yield an enolic intermediate. This analysis resolves the conflict that had linked MAL to the histidine and phenylalanine ammonia lyase family of enzymes.

AB - Methylaspartate ammonia lyase (MAL) catalyzes the magnesium-dependent reversible α,β-elimination of ammonia from L-threo-(2S,3S)-3-methylaspartic acid to mesaconic acid. The 1.3 Å MAD crystal structure of the dimeric Citrobacter amalonaticus MAL shows that each subunit comprises two domains, one of which adopts the classical TIM barrel fold, with the active site at the C-terminal end of the barrel. Despite very low sequence similarity, the structure of MAL is closely related to those of representative members of the enolase superfamily, indicating that the mechanism of MAL involves the initial abstraction of a proton α to the 3-carboxyl of (2S,3S)-3-methylasparic acid to yield an enolic intermediate. This analysis resolves the conflict that had linked MAL to the histidine and phenylalanine ammonia lyase family of enzymes.

KW - Enolase superfamily

KW - Evolution

KW - MAD phasing

KW - Methylaspartate ammonia lyase

KW - Selenomethionine

KW - X-ray crystallography

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AN - SCOPUS:0036151237

SN - 0969-2126

VL - 10

SP - 105

EP - 113

JO - Structure

JF - Structure

IS - 1

ER -

Insights into enzyme evolution revealed by the structure of methylaspartate ammonia lyase

Abstract

Keywords

Research Beacons, Institutes and Platforms

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