Crystal Structures of Methionine Adenosyltransferase Complexed with Substrates and Products Reveal the Methionine-ATP Recognition and Give Insights into the Catalytic Mechanism

González, Beatriz; Pajares, Marı́a A.; Hermoso, J.A.; Guillerm, D.; Guillerm, Georges; Sanz‐Aparicio, Julia

doi:10.1016/s0022-2836(03)00728-9

Cited by 46 publications

(77 citation statements)

References 30 publications

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“…Despite the plethora of MAT structures that have been published (10,11,(21)(22)(23) or deposited in the PDB, to date only one structure of human MATα2 (12) (1.2 Å resolution) and of the MAT(α2) 4 (βV2) 2 complex (4) (2.35-3.3 Å resolution) have been published. The mechanism of MAT enzyme function has been described for eMAT (11), and this has become the accepted mechanism for MAT enzymes.…”

Section: Discussionmentioning

confidence: 99%

“…A diverse series of structures are available for MAT enzymes from bacteria, rat, and human (4,(10)(11)(12), which, supported by a range of biochemical evidence, have provided significant insight into the enzymatic mechanism. SAMe synthesis follows an SN 2 catalytic mechanism (13,14) in which the reaction is initiated through a nucleophilic attack by the sulfur atom of methionine on the C5′ atom of ATP, which produces the intermediate tripolyphosphate (PPPi).…”

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confidence: 99%

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Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes

Murray

Antonyuk

Marina

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The principal methyl donor of the cell, S-adenosylmethionine (SAMe), is produced by the highly conserved family of methionine adenosyltranferases (MATs) via an ATP-driven process. These enzymes play an important role in the preservation of life, and their dysregulation has been tightly linked to liver and colon cancers. We present crystal structures of human MATα2 containing various bound ligands, providing a "structural movie" of the catalytic steps. High-to atomic-resolution structures reveal the structural elements of the enzyme involved in utilization of the substrates methionine and adenosine and in formation of the product SAMe. MAT enzymes are also able to produce S-adenosylethionine (SAE) from substrate ethionine. Ethionine, an S-ethyl analog of the amino acid methionine, is known to induce steatosis and pancreatitis. We show that SAE occupies the active site in a manner similar to SAMe, confirming that ethionine also uses the same catalytic site to form the product SAE.methionine adenosyltransferase | cell growth | liver cancer | X-ray crystallography | methylation

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes

Murray

Antonyuk

Marina

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Crystal structures of human MAT2A (hMAT2A, 2P02, unpublished), human MAT1A (hMAT1A, 2OBV, unpublished), and rat MAT1A (rMAT1A, 1O9T) (González et al, 2003) were used to evaluate the possible structural consequences of the two MAT2A variant allozymes. Superimposition and analysis of these structures and the computational "mutation" of Ile205 to Val205 in human MAT2A were performed with the graphics program COOT (Emsley and Cowtan, 2004).…”

Section: Matmentioning

confidence: 99%

Methionine Adenosyltransferase 2A/2B and Methylation: Gene Sequence Variation and Functional Genomics

Nordgren¹,

Peng²,

Pelleymounter

et al. 2011

Drug Metab Dispos

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ABSTRACT:Methionine adenosyltransferase (MAT) catalyzes the synthesis of Sadenosylmethionine, the major biological methyl donor. MAT1A and MAT2A encode two distinct MAT isoforms in mammals. MAT2A is expressed in nonhepatic tissues, whereas MAT1A is expressed in the liver. A third gene, MAT2B, encodes a MAT2A regulatory protein. We resequenced MAT2A and MAT2B exons, splice junctions, and flanking regions using 288 DNA samples from three ethnic groups and also imputed additional single nucleotide polymorphisms (SNPs) across both genes using data from the 1000 Genomes Project.

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“…show monomers organized in three domains formed by nonconsecutive stretches of the sequence, and the subunits interact through a large flat hydrophobic surface to form the dimers [7,[16][17][18]. Active sites, two per dimer, locate between monomers with residues of both subunits contributing to them, thus the minimum association level of active MATs is the dimer.…”

Section: Introductionmentioning

confidence: 99%

Refolding and characterization of methionine adenosyltransferase from Euglena gracilis

Garrido

Estrela

Alves

et al. 2011

Protein Expression and Purification

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Crystal Structures of Methionine Adenosyltransferase Complexed with Substrates and Products Reveal the Methionine-ATP Recognition and Give Insights into the Catalytic Mechanism

Cited by 46 publications

References 30 publications

Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes

Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes

Methionine Adenosyltransferase 2A/2B and Methylation: Gene Sequence Variation and Functional Genomics

Refolding and characterization of methionine adenosyltransferase from Euglena gracilis

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