Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity

Biochemistry
G PolekhinaM W Parker

Abstract

Maleylacetoacetate isomerase (MAAI), a key enzyme in the metabolic degradation of phenylalanine and tyrosine, catalyzes the glutathione-dependent isomerization of maleylacetoacetate to fumarylacetoacetate. Deficiencies in enzymes along the degradation pathway lead to serious diseases including phenylketonuria, alkaptonuria, and the fatal disease, hereditary tyrosinemia type I. The structure of MAAI might prove useful in the design of inhibitors that could be used in the clinical management of the latter disease. Here we report the crystal structure of human MAAI at 1.9 A resolution in complex with glutathione and a sulfate ion which mimics substrate binding. The enzyme has previously been shown to belong to the zeta class of the glutathione S-transferase (GST) superfamily based on limited sequence similarity. The structure of MAAI shows that it does adopt the GST canonical fold but with a number of functionally important differences. The structure provides insights into the molecular bases of the remarkable array of different reactions the enzyme is capable of performing including isomerization, oxygenation, dehalogenation, peroxidation, and transferase activity.

References

Jan 1, 1997·Chemical Research in Toxicology·R N Armstrong
Feb 7, 1998·The Journal of Biological Chemistry·J M Fernández-Cañón, M A Peñalva
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Mar 25, 1999·Acta Crystallographica. Section D, Biological Crystallography·R M Esnouf
Apr 25, 2000·Chemical Research in Toxicology·H F TzengM W Anders
Apr 28, 2000·The Journal of Biological Chemistry·P G BoardJ Pandit
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson

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Citations

Aug 9, 2007·Marine Biotechnology·Brian BlanchetteBal Ram Singh
Sep 10, 2011·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Thomas E EdwardsLance J Stewart
Oct 5, 2010·The Journal of Pharmacology and Experimental Therapeutics·Wenjun LiPeter W Stacpoole
Jun 8, 2002·Molecular and Cellular Biology·José Manuel Fernández-CañónMarkus Grompe
Dec 21, 2004·Human Genomics·Daniel W Nebert, Vasilis Vasiliou
Jan 15, 2014·Enzyme and Microbial Technology·Elif Oztetik, Ayse Cakir
May 16, 2014·Physical Chemistry Chemical Physics : PCCP·Hisham M DokainishJames W Gauld
May 24, 2013·The Journal of Physical Chemistry. B·Diogo Vila-ViçosaMiguel Machuqueiro
Mar 25, 2011·Drug Metabolism Reviews·Aaron Oakley
Feb 18, 2003·Pest Management Science·Frederica L TheodoulouDavid L Hallahan
Nov 6, 2012·Trends in Pharmacological Sciences·Baojian Wu, Dong Dong
Sep 2, 2008·Archives of Biochemistry and Biophysics·Tassanee Lerksuthirat, Albert J Ketterman
Aug 2, 2012·Chembiochem : a European Journal of Chemical Biology·Ellen ZandvoortGerrit J Poelarends
Feb 11, 2010·Proteins·D R LittlerP M G Curmi
Dec 4, 2012·Biochimica Et Biophysica Acta·Philip G Board, Deepthi Menon
Sep 13, 2011·Journal of Molecular Biology·Heather A KingMichael W Young
Oct 20, 2007·Journal of Molecular Biology·Brett A CromerMichael W Parker
Feb 11, 2015·Neurochemistry International·Anna Paola MazzettiMario Lo Bello
Sep 7, 2001·Toxicology and Applied Pharmacology·I R Schultz, S R Sylvester
Dec 3, 2014·Aquatic Toxicology·Branka GlisicTvrtko Smital
May 5, 2016·Pharmacogenomics·Margaret O James, Peter W Stacpoole
Apr 2, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mahsa TaebAbbas Mirshafiey
Jun 3, 2004·The Journal of Biological Chemistry·Giorgio RicciAnna Maria Caccuri
Jul 15, 2009·Drug and Alcohol Review·Carla J Treloar, Suzanne M Fraser
Oct 1, 2005·The Journal of Biological Chemistry·Eleonora CesareoMario Lo Bello

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