Structure and Mechanism of Isopropylmalate Dehydrogenase from Arabidopsis thaliana: Insights on Leucine and Aliphatic Glucosinolate Biosynthesis

Lee, Soon Goo; Nwumeh, Ronald; Jez, Joseph M.

doi:10.1074/jbc.M116.730358

Title: Structure and Mechanism of Isopropylmalate Dehydrogenase from Arabidopsis thaliana: Insights on Leucine and Aliphatic Glucosinolate Biosynthesis

Journal Article · Mon May 02 00:00:00 EDT 2016 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.M116.730358· OSTI ID:1267478

Lee, Soon Goo ^[1]; Nwumeh, Ronald ^[1]; Jez, Joseph M. ^[1]

Washington Univ., St. Louis, MO (United States)

Isopropylmalate dehydrogenase (IPMDH) and 3-(2'-methylthio)ethylmalate dehydrogenase catalyze the oxidative decarboxylation of different β-hydroxyacids in the leucine- and methionine-derived glucosinolate biosynthesis pathways, respectively, in plants. Evolution of the glucosinolate biosynthetic enzyme from IPMDH results from a single amino acid substitution that alters substrate specificity. Here, we present the x-ray crystal structures of Arabidopsis thaliana IPMDH2 (AtIPMDH2) in complex with either isopropylmalate and Mg²⁺ or NAD⁺. These structures reveal conformational changes that occur upon ligand binding and provide insight on the active site of the enzyme. The x-ray structures and kinetic analysis of site-directed mutants are consistent with a chemical mechanism in which Lys-232 activates a water molecule for catalysis. Furthermore, structural analysis of the AtIPMDH2 K232M mutant and isothermal titration calorimetry supports a key role of Lys-232 in the reaction mechanism. This study suggests that IPMDH-like enzymes in both leucine and glucosinolate biosynthesis pathways use a common mechanism and that members of the β-hydroxyacid reductive decarboxylase family employ different active site features for similar reactions.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Science Foundation (NSF); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: MCB-0904215; AC02–06CH11357

OSTI ID:: 1267478

Journal Information:: Journal of Biological Chemistry, Vol. 291, Issue 26; ISSN 0021-9258

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

Citation Metrics:

Cited by: 11 works

Citation information provided by
Web of Science

References (30)

Crystal structures of Escherichia coli and Salmonella typhimurium 3-isopropylmalate dehydrogenase and comparison with their thermophilic counterpart from Thermus thermophilus Wallon, Gerlind; Kryger, Gitay; Lovett, Susan T. Journal of Molecular Biology, Vol. 266, Issue 5 https://doi.org/10.1006/jmbi.1996.0797	journal	March 1997
Structure of 3–isopropylmalate dehydrogenase in complex with NAD+: ligand–induced loop closing and mechanism for cofactor specificity Hurley, James H.; Dean, Antony M. Structure, Vol. 2, Issue 11 https://doi.org/10.1016/S0969-2126(94)00104-9	journal	November 1994
A Lysine-Tyrosine Pair Carries Out Acid−Base Chemistry in the Metal Ion-Dependent Pyridine Dinucleotide-Linked β-Hydroxyacid Oxidative Decarboxylases ^† Aktas, Deniz F.; Cook, Paul F. Biochemistry, Vol. 48, Issue 16 https://doi.org/10.1021/bi8022976	journal	April 2009
Crystal Structure of Tetrameric Homoisocitrate Dehydrogenase from an Extreme Thermophile, Thermus thermophilus: Involvement of Hydrophobic Dimer-Dimer Interaction in Extremely High Thermotolerance Miyazaki, J.; Asada, K.; Fushinobu, S. Journal of Bacteriology, Vol. 187, Issue 19 https://doi.org/10.1128/JB.187.19.6779-6788.2005	journal	September 2005
Arabidopsis Branched-Chain Aminotransferase 3 Functions in Both Amino Acid and Glucosinolate Biosynthesis Knill, Tanja; Schuster, Joachim; Reichelt, Michael Plant Physiology, Vol. 146, Issue 3 https://doi.org/10.1104/pp.107.111609	journal	December 2007
Functional characterization of Arabidopsis thaliana isopropylmalate dehydrogenases reveals their important roles in gametophyte development He, Yan; Chen, Liqun; Zhou, Yuan New Phytologist, Vol. 189, Issue 1 https://doi.org/10.1111/j.1469-8137.2010.03460.x	journal	September 2010
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Cloning and expression analysis of β-isopropylmalate dehydrogenase from potato Jackson, Stephen D.; Sonnewald, Uwe; Willmitzer, Lothar Molecular and General Genetics MGG, Vol. 236-236, Issue 2-3 https://doi.org/10.1007/BF00277127	journal	January 1993
Three-dimensional structure of a highly thermostable enzyme, 3-isopropylmalate dehydrogenase of Thermus thermophilus at 2.2 Å resolution Imada, Katsumi; Sato, Mamoru; Tanaka, Nobuo Journal of Molecular Biology, Vol. 222, Issue 3 https://doi.org/10.1016/0022-2836(91)90508-4	journal	December 1991
Dual Role of the Active Site Residues of Thermus thermophilus 3-Isopropylmalate Dehydrogenase: Chemical Catalysis and Domain Closure Gráczer, Éva; Szimler, Tamás; Garamszegi, Anita Biochemistry, Vol. 55, Issue 3 https://doi.org/10.1021/acs.biochem.5b00839	journal	January 2016
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Glucosinolate structures in evolution Agerbirk, Niels; Olsen, Carl Erik Phytochemistry, Vol. 77 https://doi.org/10.1016/j.phytochem.2012.02.005	journal	May 2012
MAM3 Catalyzes the Formation of All Aliphatic Glucosinolate Chain Lengths in Arabidopsis Textor, Susanne; de Kraker, Jan-Willem; Hause, Bettina Plant Physiology, Vol. 144, Issue 1 https://doi.org/10.1104/pp.106.091579	journal	March 2007
Tyr-139 in Thermus thermophilus 3-isopropylmalate dehydrogenase is involved in catalytic function Miyazaki, Kentaro; Oshima, Tairo FEBS Letters, Vol. 332, Issue 1-2 https://doi.org/10.1016/0014-5793(93)80478-D	journal	October 1993
Seeing double: gene duplication and diversification in plant secondary metabolism Ober, Dietrich Trends in Plant Science, Vol. 10, Issue 9 https://doi.org/10.1016/j.tplants.2005.07.007	journal	September 2005
Natural diversity and adaptation in plant secondary metabolism Kroymann, Juergen Current Opinion in Plant Biology, Vol. 14, Issue 3 https://doi.org/10.1016/j.pbi.2011.03.021	journal	June 2011
A Catalytic Triad Is Responsible for Acid−Base Chemistry in the Ascaris suum NAD−Malic Enzyme ^† Karsten, William E.; Liu, Dali; Rao, G. S. Jagannatha Biochemistry, Vol. 44, Issue 9 https://doi.org/10.1021/bi047826o	journal	March 2005
Biosynthesis of methionine-derived glucosinolates in Arabidopsis thaliana : recombinant expression and characterization of methylthioalkylmalate synthase, the condensing enzyme of the chain-elongation cycle Textor, Susanne; Bartram, Stefan; Kroymann, J�rgen Planta, Vol. 218, Issue 6 https://doi.org/10.1007/s00425-003-1184-3	journal	April 2004
NMRPipe: A multidimensional spectral processing system based on UNIX pipes Delaglio, Frank; Grzesiek, Stephan; Vuister, GeertenW. Journal of Biomolecular NMR, Vol. 6, Issue 3 https://doi.org/10.1007/BF00197809	journal	November 1995
Biology and Biochemistry of Glucosinolates Halkier, Barbara Ann; Gershenzon, Jonathan Annual Review of Plant Biology, Vol. 57, Issue 1 https://doi.org/10.1146/annurev.arplant.57.032905.105228	journal	June 2006
Glutamate 190 Is a General Acid Catalyst in the 6-Phosphogluconate-Dehydrogenase-Catalyzed Reaction ^† Karsten, William E.; Chooback, Lilian; Cook, Paul F. Biochemistry, Vol. 37, Issue 45 https://doi.org/10.1021/bi9812827	journal	November 1998
Structure of 3-isopropylmalate dehydrogenase in complex with 3-isopropylmalate at 2.0 å resolution: the role of Glu88 in the unique substrate-recognition mechanism Imada, Katsumi; Inagaki, Kenji; Matsunami, Hideyuki Structure, Vol. 6, Issue 8 https://doi.org/10.1016/S0969-2126(98)00099-9	journal	August 1998
BRANCHED-CHAIN AMINOTRANSFERASE4 Is Part of the Chain Elongation Pathway in the Biosynthesis of Methionine-Derived Glucosinolates in Arabidopsis Schuster, Joachim; Knill, Tanja; Reichelt, Michael The Plant Cell, Vol. 18, Issue 10 https://doi.org/10.1105/tpc.105.039339	journal	October 2006
Allosteric Motions in Structures of Yeast NAD ⁺ -specific Isocitrate Dehydrogenase Taylor, Alexander B.; Hu, Gang; Hart, P. John Journal of Biological Chemistry, Vol. 283, Issue 16 https://doi.org/10.1074/jbc.M708719200	journal	February 2008
Ligand-Induced Changes in the Conformation of 3-Isopropylmalate Dehydrogenase from Thermus thermophilus Kadono, Shojiro; Sakurai, Masahiro; Moriyama, Hideaki The Journal of Biochemistry, Vol. 118, Issue 4 https://doi.org/10.1093/oxfordjournals.jbchem.a124975	journal	October 1995
Structural and Functional Evolution of Isopropylmalate Dehydrogenases in the Leucine and Glucosinolate Pathways of Arabidopsis thaliana He, Yan; Galant, Ashley; Pang, Qiuying Journal of Biological Chemistry, Vol. 286, Issue 33 https://doi.org/10.1074/jbc.M111.262519	journal	June 2011
Cloning of a cDNA for rape chloroplast 3-isopropylmalate dehydrogenase by genetic complementation in yeast Ellerstr�m, Mats; Josefsson, Lars -G�ran; Rask, Lars Plant Molecular Biology, Vol. 18, Issue 3 https://doi.org/10.1007/BF00040671	journal	February 1992
Cloning of cDNAs Encoding Isopropylmalate Dehydrogenase from Arabidopsis thaliana and Accumulation Patterns of Their Transcripts Nozawa, Akira; Takano, Junpei; Miwa, Kyoko Bioscience, Biotechnology, and Biochemistry, Vol. 69, Issue 4 https://doi.org/10.1271/bbb.69.806	journal	January 2005
A redox-active isopropylmalate dehydrogenase functions in the biosynthesis of glucosinolates and leucine in Arabidopsis He, Yan; Mawhinney, Thomas P.; Preuss, Mary L. The Plant Journal, Vol. 60, Issue 4 https://doi.org/10.1111/j.1365-313X.2009.03990.x	journal	November 2009
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007

Similar Records

Structural and functional evolution of isopropylmalate dehydrogenases in the leucine and glucosinolate pathways of Arabidopsis thaliana

Journal Article · Wed Oct 24 00:00:00 EDT 2012 · J. Biol. Chem. · OSTI ID:1267478

He, Yan; Galant, Ashley; Pang, Qiuying; +4 more

Crystal structure of homoisocitrate dehydrogenase from Schizosaccharomyces pombe

Journal Article · Wed Sep 18 00:00:00 EDT 2013 · Proteins · OSTI ID:1267478

Bulfer, Stacie L.; Hendershot, Jenna M.; Trievel, Raymond C.

Influence of isopropylmalate synthase Os IPMS 1 on seed vigour associated with amino acid and energy metabolism in rice

Journal Article · Mon Jul 16 00:00:00 EDT 2018 · Plant Biotechnology Journal · OSTI ID:1267478

He, Yongqi; Cheng, Jinping; He, Ying; +5 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
enzyme
plant biochemistry
protein evolution
protein structure
x-ray crystallography
reaction mechanism

Title: Structure and Mechanism of Isopropylmalate Dehydrogenase from Arabidopsis thaliana: Insights on Leucine and Aliphatic Glucosinolate Biosynthesis

Citation Formats

References (30)

Similar Records

Related Subjects