Structure-function relationships in methionine adenosyltransferases |
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Authors: | G. D. Markham M. A. Pajares |
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Affiliation: | (1) Institute for Cancer Research, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA;(2) Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM), Arturo Duperier 4, 28029 Madrid, Spain |
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Abstract: | Methionine adenosyltransferases (MATs) are the family of enzymes that synthesize the main biological methyl donor, S-adenosylmethionine. The high sequence conservation among catalytic subunits from bacteria and eukarya preserves key residues that control activity and oligomerization, which is reflected in the protein structure. However, structural differences among complexes with substrates and products have led to proposals of several reaction mechanisms. In parallel, folding studies begin to explain how the three intertwined domains of the catalytic subunit are produced, and to highlight the importance of certain intermediates in attaining the active final conformation. This review analyzes the available structural data and proposes a consensus interpretation that facilitates an understanding of the pathological problems derived from impairment of MAT function. In addition, new research opportunities directed toward clarification of aspects that remain obscure are also identified. Received 22 August 2008; received after revision 22 September 2008; accepted 26 September 2008 |
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Keywords: | KeywordHeading" >. Methionine adenosyltransferase S-adenosylmethionine synthetase crystal structure reaction mechanism folding mutants hepatic disease |
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