The origin and evolution of human glutaminases and their atypical C-terminal ankyrin repeats
Abstract
On the basis of tissue-specific enzyme activity and inhibition by catalytic products, Hans Krebs first demonstrated the existence of multiple glutaminases in mammals. Currently, two human genes are known to encode at least four glutaminase isoforms. But, the phylogeny of these medically relevant enzymes remains unclear, prompting us to investigate their origin and evolution. Using prokaryotic and eukaryotic glutaminase sequences, we built a phylogenetic tree whose topology suggested that the multidomain architecture was inherited from bacterial ancestors, probably simultaneously with the hosting of the proto-mitochondrion endosymbiont. We propose an evolutionary model wherein the appearance of the most active enzyme isoform, glutaminase C (GAC), which is expressed in many cancers, was a late retrotransposition event that occurred in fishes from the Chondrichthyes class. The ankyrin (ANK) repeats in the glutaminases were acquired early in their evolution. In order to obtain information on ANK folding, we solved two high-resolution structures of the ANK repeat-containing C termini of both kidney-type glutaminase (KGA) and GLS2 isoforms (glutaminase B and liver-type glutaminase). We also found that the glutaminase ANK repeats form unique intramolecular contacts through two highly conserved motifs; curiously, this arrangement occludes a region usually involved in ANK-mediated protein-protein interactions. We also solved themore »
- Authors:
-
- National Center for Research in Energy and Materials, Sao Paulo (Brazil). National Lab. of Biosciences
- National Center for Research in Energy and Materials, Sao Paulo (Brazil). National Lab. of Biosciences; Univ. of Oxford (United Kingdom). Structural Genomics Consortium
- National Center for Research in Energy and Materials, Sao Paulo (Brazil). National Lab. of Nanotechnologies
- Univ. of Oxford (United Kingdom). Structural Genomics Consortium
- SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource
- Publication Date:
- Research Org.:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1374373
- Grant/Contract Number:
- AC02-76SF00515; 2014/20673–2; 2015/25832–4; 2014/19518–2; 2014/12663–7; 2014/17820–3; 2013/05668–0
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Biological Chemistry
- Additional Journal Information:
- Journal Volume: 292; Journal Issue: 27; Journal ID: ISSN 0021-9258
- Publisher:
- American Society for Biochemistry and Molecular Biology
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; cancer; glutaminase; human; metabolism; x-ray crystallography; isoform
Citation Formats
Pasquali, Camila Cristina, Islam, Zeyaul, Adamoski, Douglas, Ferreira, Igor Monteze, Righeto, Ricardo Diogo, Bettini, Jefferson, Portugal, Rodrigo Villares, Yue, Wyatt Wai-yin, Gonzalez, Ana, Dias, Sandra Martha Gomes, and Ambrosio, Andre Luis Berteli. The origin and evolution of human glutaminases and their atypical C-terminal ankyrin repeats. United States: N. p., 2017.
Web. doi:10.1074/jbc.M117.787291.
Pasquali, Camila Cristina, Islam, Zeyaul, Adamoski, Douglas, Ferreira, Igor Monteze, Righeto, Ricardo Diogo, Bettini, Jefferson, Portugal, Rodrigo Villares, Yue, Wyatt Wai-yin, Gonzalez, Ana, Dias, Sandra Martha Gomes, & Ambrosio, Andre Luis Berteli. The origin and evolution of human glutaminases and their atypical C-terminal ankyrin repeats. United States. https://doi.org/10.1074/jbc.M117.787291
Pasquali, Camila Cristina, Islam, Zeyaul, Adamoski, Douglas, Ferreira, Igor Monteze, Righeto, Ricardo Diogo, Bettini, Jefferson, Portugal, Rodrigo Villares, Yue, Wyatt Wai-yin, Gonzalez, Ana, Dias, Sandra Martha Gomes, and Ambrosio, Andre Luis Berteli. Fri .
"The origin and evolution of human glutaminases and their atypical C-terminal ankyrin repeats". United States. https://doi.org/10.1074/jbc.M117.787291. https://www.osti.gov/servlets/purl/1374373.
@article{osti_1374373,
title = {The origin and evolution of human glutaminases and their atypical C-terminal ankyrin repeats},
author = {Pasquali, Camila Cristina and Islam, Zeyaul and Adamoski, Douglas and Ferreira, Igor Monteze and Righeto, Ricardo Diogo and Bettini, Jefferson and Portugal, Rodrigo Villares and Yue, Wyatt Wai-yin and Gonzalez, Ana and Dias, Sandra Martha Gomes and Ambrosio, Andre Luis Berteli},
abstractNote = {On the basis of tissue-specific enzyme activity and inhibition by catalytic products, Hans Krebs first demonstrated the existence of multiple glutaminases in mammals. Currently, two human genes are known to encode at least four glutaminase isoforms. But, the phylogeny of these medically relevant enzymes remains unclear, prompting us to investigate their origin and evolution. Using prokaryotic and eukaryotic glutaminase sequences, we built a phylogenetic tree whose topology suggested that the multidomain architecture was inherited from bacterial ancestors, probably simultaneously with the hosting of the proto-mitochondrion endosymbiont. We propose an evolutionary model wherein the appearance of the most active enzyme isoform, glutaminase C (GAC), which is expressed in many cancers, was a late retrotransposition event that occurred in fishes from the Chondrichthyes class. The ankyrin (ANK) repeats in the glutaminases were acquired early in their evolution. In order to obtain information on ANK folding, we solved two high-resolution structures of the ANK repeat-containing C termini of both kidney-type glutaminase (KGA) and GLS2 isoforms (glutaminase B and liver-type glutaminase). We also found that the glutaminase ANK repeats form unique intramolecular contacts through two highly conserved motifs; curiously, this arrangement occludes a region usually involved in ANK-mediated protein-protein interactions. We also solved the crystal structure of full-length KGA and present a small-angle X-ray scattering model for full-length GLS2. These structures explain these proteins' compromised ability to assemble into catalytically active supra-tetrameric filaments, as previously shown for GAC. Collectively, these results provide information about glutaminases that may aid in the design of isoform-specific glutaminase inhibitors.},
doi = {10.1074/jbc.M117.787291},
journal = {Journal of Biological Chemistry},
number = 27,
volume = 292,
place = {United States},
year = {Fri May 19 00:00:00 EDT 2017},
month = {Fri May 19 00:00:00 EDT 2017}
}
Web of Science
Works referenced in this record:
The BioPlex Network: A Systematic Exploration of the Human Interactome
journal, July 2015
- Huttlin, Edward L.; Ting, Lily; Bruckner, Raphael J.
- Cell, Vol. 162, Issue 2
Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer
journal, November 2009
- DeBerardinis, R. J.; Cheng, T.
- Oncogene, Vol. 29, Issue 3
The Draft Genome of Ciona intestinalis: Insights into Chordate and Vertebrate Origins
journal, December 2002
- Dehal, P.
- Science, Vol. 298, Issue 5601
Phosphate-dependent glutaminase from rat kidney
journal, January 1976
- Curthoys, Norman P.; Kuhlenschmidt, Theresa; Godfrey, Susan S.
- Archives of Biochemistry and Biophysics, Vol. 172, Issue 1
Glutaminase 2 negatively regulates the PI3K/AKT signaling and shows tumor suppression activity in human hepatocellular carcinoma
journal, March 2014
- Liu, Juan; Zhang, Cen; Lin, Meihua
- Oncotarget, Vol. 5, Issue 9
The zebrafish reference genome sequence and its relationship to the human genome
journal, April 2013
- Howe, Kerstin; Clark, Matthew D.; Torroja, Carlos F.
- Nature, Vol. 496, Issue 7446
Determination of the regularization parameter in indirect-transform methods using perceptual criteria
journal, August 1992
- Svergun, D. I.
- Journal of Applied Crystallography, Vol. 25, Issue 4, p. 495-503
Functional and Structural Characterization of Four Glutaminases from Escherichia coli and Bacillus subtilis †
journal, May 2008
- Brown, Greg; Singer, Alex; Proudfoot, Michael
- Biochemistry, Vol. 47, Issue 21
Crystal Structure of the Yeast Ribosomal Protein rpS3 in Complex with Its Chaperone Yar1
journal, November 2013
- Holzer, Sandro; Ban, Nenad; Klinge, Sebastian
- Journal of Molecular Biology, Vol. 425, Issue 22
PRIMUS: a Windows PC-based system for small-angle scattering data analysis
journal, September 2003
- Konarev, Petr V.; Volkov, Vladimir V.; Sokolova, Anna V.
- Journal of Applied Crystallography, Vol. 36, Issue 5, p. 1277-1282
REFMAC 5 dictionary: organization of prior chemical knowledge and guidelines for its use
journal, November 2004
- Vagin, Alexei A.; Steiner, Roberto A.; Lebedev, Andrey A.
- Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12
Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction
journal, November 2008
- Wise, D. R.; DeBerardinis, R. J.; Mancuso, A.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 48
Active Glutaminase C Self-assembles into a Supratetrameric Oligomer That Can Be Disrupted by an Allosteric Inhibitor
journal, August 2013
- Ferreira, Amanda Petrina Scotá; Cassago, Alexandre; Gonçalves, Kaliandra de Almeida
- Journal of Biological Chemistry, Vol. 288, Issue 39
ATSAS 2.1 – towards automated and web-supported small-angle scattering data analysis
journal, April 2007
- Petoukhov, Maxim V.; Konarev, Peter V.; Kikhney, Alexey G.
- Journal of Applied Crystallography, Vol. 40, Issue s1
From Krebs to clinic: glutamine metabolism to cancer therapy
journal, July 2016
- Altman, Brian J.; Stine, Zachary E.; Dang, Chi V.
- Nature Reviews Cancer, Vol. 16, Issue 10
The structural basis of integrin-linked kinase-PINCH interactions
journal, December 2008
- Chiswell, B. P.; Zhang, R.; Murphy, J. W.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 52
How good are my data and what is the resolution?
journal, June 2013
- Evans, Philip R.; Murshudov, Garib N.
- Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7
The amphioxus genome and the evolution of the chordate karyotype
journal, June 2008
- Putnam, Nicholas H.; Butts, Thomas; Ferrier, David E. K.
- Nature, Vol. 453, Issue 7198
JPred4: a protein secondary structure prediction server
journal, April 2015
- Drozdetskiy, Alexey; Cole, Christian; Procter, James
- Nucleic Acids Research, Vol. 43, Issue W1
Mapping the Tree of Life: Progress and Prospects
journal, November 2009
- Pace, N. R.
- Microbiology and Molecular Biology Reviews, Vol. 73, Issue 4
The ankyrin repeat as molecular architecture for protein recognition
journal, June 2004
- Mosavi, Leila K.; Cammett, Tobin J.; Desrosiers, Daniel C.
- Protein Science, Vol. 13, Issue 6
Nuclear Localization of L-type Glutaminase in Mammalian Brain
journal, August 2002
- Olalla, Lucı́a; Gutiérrez, Antonia; Campos, José A.
- Journal of Biological Chemistry, Vol. 277, Issue 41
DendroPy: a Python library for phylogenetic computing
journal, April 2010
- Sukumaran, J.; Holder, M. T.
- Bioinformatics, Vol. 26, Issue 12
Restricted Diversity of Antigen Binding Residues of Antibodies Revealed by Computational Alanine Scanning of 227 Antibody–Antigen Complexes
journal, November 2014
- Robin, Gautier; Sato, Yoshiteru; Desplancq, Dominique
- Journal of Molecular Biology, Vol. 426, Issue 22
The NF-κB member p65 controls glutamine metabolism through miR-23a
journal, September 2012
- Rathore, Moeez G.; Saumet, Anne; Rossi, Jean-François
- The International Journal of Biochemistry & Cell Biology, Vol. 44, Issue 9
The Control of the Metabolic Switch in Cancers by Oncogenes and Tumor Suppressor Genes
journal, December 2010
- Levine, A. J.; Puzio-Kuter, A. M.
- Science, Vol. 330, Issue 6009
Full-Length Human Glutaminase in Complex with an Allosteric Inhibitor
journal, December 2011
- DeLaBarre, Byron; Gross, Stefan; Fang, Cheng
- Biochemistry, Vol. 50, Issue 50
Mammalian Glutaminase Gls2 Gene Encodes Two Functional Alternative Transcripts by a Surrogate Promoter Usage Mechanism
journal, June 2012
- Martín-Rufián, Mercedes; Tosina, Marta; Campos-Sandoval, José A.
- PLoS ONE, Vol. 7, Issue 6
Inference of Macromolecular Assemblies from Crystalline State
journal, September 2007
- Krissinel, Evgeny; Henrick, Kim
- Journal of Molecular Biology, Vol. 372, Issue 3
XDS
journal, January 2010
- Kabsch, Wolfgang
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2
GenBank
journal, November 2015
- Clark, Karen; Karsch-Mizrachi, Ilene; Lipman, David J.
- Nucleic Acids Research, Vol. 44, Issue D1
UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004
- Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
- Journal of Computational Chemistry, Vol. 25, Issue 13
Targeting Mitochondrial Glutaminase Activity Inhibits Oncogenic Transformation
journal, September 2010
- Wang, Jian-Bin; Erickson, Jon W.; Fuji, Reina
- Cancer Cell, Vol. 18, Issue 3
Opposing roles of glutaminase isoforms in determining glioblastoma cell phenotype
journal, September 2015
- Szeliga, Monika; Albrecht, Jan
- Neurochemistry International, Vol. 88
Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function
journal, April 2010
- Hu, W.; Zhang, C.; Wu, R.
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 16
Mitochondrial localization and structure-based phosphate activation mechanism of Glutaminase C with implications for cancer metabolism
journal, January 2012
- Cassago, A.; Ferreira, A. P. S.; Ferreira, I. M.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 4
RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies
journal, January 2014
- Stamatakis, Alexandros
- Bioinformatics, Vol. 30, Issue 9
TranspoGene and microTranspoGene: transposed elements influence on the transcriptome of seven vertebrates and invertebrates
journal, November 2007
- Levy, Asaf; Sela, Noa; Ast, Gil
- Nucleic Acids Research, Vol. 36, Issue suppl_1
Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a
journal, September 1998
- Russo, Alicia A.; Tong, Lily; Lee, Jie-Oh
- Nature, Vol. 395, Issue 6699
A time-efficient, linear-space local similarity algorithm
journal, September 1991
- Huang, Xiaoqiu; Miller, Webb
- Advances in Applied Mathematics, Vol. 12, Issue 3
EMAN2: An extensible image processing suite for electron microscopy
journal, January 2007
- Tang, Guang; Peng, Liwei; Baldwin, Philip R.
- Journal of Structural Biology, Vol. 157, Issue 1
Metabolism of amino-acids
journal, August 1935
- Krebs, Hans Adolf
- Biochemical Journal, Vol. 29, Issue 8
The ankyrin repeat: a diversity of interactions on a common structural framework
journal, August 1999
- Sedgwick, Steven G.; Smerdon, Stephen J.
- Trends in Biochemical Sciences, Vol. 24, Issue 8
Iterative Stable Alignment and Clustering of 2D Transmission Electron Microscope Images
journal, February 2012
- Yang, Zhengfan; Fang, Jia; Chittuluru, Johnathan
- Structure, Vol. 20, Issue 2
Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species
journal, March 2010
- Suzuki, S.; Tanaka, T.; Poyurovsky, M. V.
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 16
phangorn: phylogenetic analysis in R
journal, December 2010
- Schliep, Klaus Peter
- Bioinformatics, Vol. 27, Issue 4
Features and development of Coot
journal, March 2010
- Emsley, P.; Lohkamp, B.; Scott, W. G.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
The oncogenic transcription factor c-Jun regulates glutaminase expression and sensitizes cells to glutaminase-targeted therapy
journal, April 2016
- Lukey, Michael J.; Greene, Kai Su; Erickson, Jon W.
- Nature Communications, Vol. 7, Issue 1
PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
Structure Function Studies of Vaccinia Virus Host Range Protein K1 Reveal a Novel Functional Surface for Ankyrin Repeat Proteins
journal, January 2010
- Li, Y.; Meng, X.; Xiang, Y.
- Journal of Virology, Vol. 84, Issue 7
The Genome of the Western Clawed Frog Xenopus tropicalis
journal, April 2010
- Hellsten, U.; Harland, R. M.; Gilchrist, M. J.
- Science, Vol. 328, Issue 5978
Anaphase-promoting complex/cyclosome-Cdh1 coordinates glycolysis and glutaminolysis with transition to S phase in human T lymphocytes
journal, October 2010
- Colombo, S. L.; Palacios-Callender, M.; Frakich, N.
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 44
Elephant shark genome provides unique insights into gnathostome evolution
journal, January 2014
- Venkatesh, Byrappa; Lee, Alison P.; Ravi, Vydianathan
- Nature, Vol. 505, Issue 7482
Structure and Asn-Pro-Phe Binding Pocket of the Eps15 Homology Domain
journal, August 1998
- de Beer, T.
- Science, Vol. 281, Issue 5381
Expression of functional human glutaminase in baculovirus system: Affinity purification, kinetic and molecular characterization
journal, January 2007
- Campos-Sandoval, José A.; López de la Oliva, Amada R.; Lobo, Carolina
- The International Journal of Biochemistry & Cell Biology, Vol. 39, Issue 4
Silencing of GLS and overexpression of GLS2 genes cooperate in decreasing the proliferation and viability of glioblastoma cells
journal, October 2013
- Szeliga, Monika; Bogacińska-Karaś, Małgorzata; Różycka, Aleksandra
- Tumor Biology, Vol. 35, Issue 3
SDT: A Virus Classification Tool Based on Pairwise Sequence Alignment and Identity Calculation
journal, September 2014
- Muhire, Brejnev Muhizi; Varsani, Arvind; Martin, Darren Patrick
- PLoS ONE, Vol. 9, Issue 9
Experimental phasing with SHELXC / D / E : combining chain tracing with density modification
journal, March 2010
- Sheldrick, George M.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
Consensus-derived structural determinants of the ankyrin repeat motif
journal, December 2002
- Mosavi, L. K.; Minor, D. L.; Peng, Z. -y.
- Proceedings of the National Academy of Sciences, Vol. 99, Issue 25
MUSCLE: multiple sequence alignment with high accuracy and high throughput
journal, March 2004
- Edgar, R. C.
- Nucleic Acids Research, Vol. 32, Issue 5, p. 1792-1797
Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution
journal, February 2013
- Smith, Jeramiah J.; Kuraku, Shigehiro; Holt, Carson
- Nature Genetics, Vol. 45, Issue 4
Regulation of Glutaminase Activity and Glutamine Metabolism
journal, July 1995
- Curthoys, Norman P.; Watford, Malcolm
- Annual Review of Nutrition, Vol. 15, Issue 1
VARP Is Recruited on to Endosomes by Direct Interaction with Retromer, Where Together They Function in Export to the Cell Surface
journal, June 2014
- Hesketh, Geoffrey G.; Pérez-Dorado, Inmaculada; Jackson, Lauren P.
- Developmental Cell, Vol. 29, Issue 5
Glutaminase 2 is a novel negative regulator of small GTPase Rac1 and mediates p53 function in suppressing metastasis
journal, January 2016
- Zhang, Cen; Liu, Juan; Zhao, Yuhan
- eLife, Vol. 5
Two Distinct Mechanisms for Actin Capping Protein Regulation—Steric and Allosteric Inhibition
journal, July 2010
- Takeda, Shuichi; Minakata, Shiho; Koike, Ryotaro
- PLoS Biology, Vol. 8, Issue 7
A Genomic Perspective on Protein Families
journal, October 1997
- Tatusov, R. L.
- Science, Vol. 278, Issue 5338
Ohno's dilemma: Evolution of new genes under continuous selection
journal, October 2007
- Bergthorsson, U.; Andersson, D. I.; Roth, J. R.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 43
Novel mechanism of inhibition of rat kidney-type glutaminase by bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES)
journal, August 2007
- Robinson, Mary M.; Mcbryant, Steven J.; Tsukamoto, Takashi
- Biochemical Journal, Vol. 406, Issue 3
Expression of the scaffolding PDZ protein glutaminase-interacting protein in mammalian brain
journal, January 2008
- Olalla, Lucía; Gutiérrez, Antonia; Jiménez, Antonio J.
- Journal of Neuroscience Research, Vol. 86, Issue 2
Phaser crystallographic software
journal, July 2007
- McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
- Journal of Applied Crystallography, Vol. 40, Issue 4
Intracellular free amino acid concentration in human muscle tissue.
journal, June 1974
- Bergström, J.; Fürst, P.; Norée, L. O.
- Journal of Applied Physiology, Vol. 36, Issue 6
Cloning and analysis of unique human glutaminase isoforms generated by tissue-specific alternative splicing
journal, August 1999
- Elgadi, Khaled M.; Meguid, Robert A.; Qian, Ming
- Physiological Genomics, Vol. 1, Issue 2
Reproductive Endocrinology of Fish
book, January 1987
- Scott, A. P.
- Fundamentals of Comparative Vertebrate Endocrinology
Works referencing / citing this record:
The membrane binding and deformation property of vaccinia virus K1 ankyrin repeat domain protein
journal, February 2020
- Kitamata, Manabu; Hotta, Mitsukuni; Hamada‐Nakahara, Sayaka
- Genes to Cells, Vol. 25, Issue 3