Dinesh Christendat

faculty_img Academic Title: Associate Professor

Campus: St. George

CSB Appointment: Full

Primary Undergraduate Department:
Cell & Systems Biology

Graduate Programs:
Cell & Systems Biology
 
Titles and Honors:
Academic or Administrative Appointments:
Education:
Ph.D. Concordia University

 

Mailing Address
Department of Cell & Systems Biology
University of Toronto
25 Willcocks St.
Toronto, ON M5S 3B2
Canada

 

Contact Information
Office phone: 416-946-8373
Office: ESC 4052
Lab: ESC 4045
Lab phone: 416-946-8436
Email: dinesh.christendat@utoronto.ca
URL: http://christendat.csb.utoronto.ca

 

Research Areas
Biotechnology
Metabolomics
Molecular Biology
Plant Biology
Proteomics
Structural Biology

 

Research
 Plants produce a tremendous variety of aromatic compounds compared to other living organisms. Most of these compounds, referred to as central metabolites, are synthesized from a product of the shikimate pathway. Central metabolites are important for the structural integrity of plants and their protection from invading organisms. Other central metabolites include flavonoids and isoflavonoids, which are potential antioxidants with important nutritional benefits to humans. The regulation of the shikimate pathway is highly coordinated with the biosynthesis of these metabolites in plants. Some questions being addressed in our lab are: What are some of the biological cues that are involved in the regulation of the pathway? How can we take advantage of these regulatory processes to stimulate the shikimate pathway to enhance the biosynthesis of certain classes of central metabolites, especially those that are of nutritional importance?

The shikimate pathway is also an attractive target for drug development because it is absent in humans, but is essential for the survival of microbes, fungi and likely apicomplexan parasites. These parasites include, Plasmodium falciparum, associated with the deadliest form of malaria, and Toxoplasma gondii, implicated in psychological disorders and toxoplasmosis. We are actively studying compounds that are potential inhibitors of enzymes of the shikimate pathway with the aim of developing novel drug compounds. As a protein biochemistry group, we utilize biochemical and biophysical approaches, such as recombinant protein production, protein modification, enzyme kinetics, protein crystallography, protein ligand screening, structural biology, proteomics, etc. to understand how proteins function and how we can modulate their activity.

 

Publications

2014

Top
Isolation and molecular characterization of the shikimate dehydrogenase domain from the Toxoplasma gondii AROM complex.Peek J, Castiglione G, Shi T, Christendat D.Mol. Biochem. Parasitol. 2014 Mar-Apr;194(1-2):16-9
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Identification of Novel Polyphenolic Inhibitors of Shikimate Dehydrogenase (AroE).Peek J, Shi T, Christendat D.J Biomol Screen 2014 Mar;19(7):1090-1098
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2013

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Crystal structure and biochemical analyses reveal that the Arabidopsis triphosphate tunnel metalloenzyme AtTTM3 is a tripolyphosphatase involved in root development.Moeder W, Garcia-Petit C, Ung H, Fucile G, Samuel MA, Christendat D, Yoshioka K.Plant J. 2013 Nov;76(4):615-26
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Sequencing and annotation of the Ophiostoma ulmi genome.Khoshraftar S, Hung S, Khan S, Gong Y, Tyagi V, Parkinson J, Sain M, Moses AM, Christendat D.BMC Genomics 2013;14:162
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Insights into the function of RifI2: structural and biochemical investigation of a new shikimate dehydrogenase family protein.Peek J, Garcia C, Lee J, Christendat D.Biochim. Biophys. Acta 2013 Feb;1834(2):516-23
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2011

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Structural and mechanistic analysis of a novel class of shikimate dehydrogenases: evidence for a conserved catalytic mechanism in the shikimate dehydrogenase family.Peek J, Lee J, Hu S, Senisterra G, Christendat D.Biochemistry 2011 Oct;50(40):8616-27
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Structural and biochemical investigation of two Arabidopsis shikimate kinases: the heat-inducible isoform is thermostable.Fucile G, Garcia C, Carlsson J, Sunnerhagen M, Christendat D.Protein Sci. 2011 Jul;20(7):1125-36
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ePlant and the 3D data display initiative: integrative systems biology on the world wide web.Fucile G, Di Biase D, Nahal H, La G, Khodabandeh S, Chen Y, Easley K, Christendat D, Kelley L, Provart NJ.PLoS ONE 2011;6(1):e15237
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2009

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The crystal structure of Aquifex aeolicus prephenate dehydrogenase reveals the mode of tyrosine inhibition.Sun W, Shahinas D, Bonvin J, Hou W, Kimber MS, Turnbull J, Christendat D.J. Biol. Chem. 2009 May;284(19):13223-32
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2008

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Evolutionary diversification of plant shikimate kinase gene duplicates.Fucile G, Falconer S, Christendat D.PLoS Genet. 2008 Dec;4(12):e1000292
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A phylogenomic analysis of the shikimate dehydrogenases reveals broadscale functional diversification and identifies one functionally distinct subclass.Singh S, Stavrinides J, Christendat D, Guttman DS.Mol. Biol. Evol. 2008 Oct;25(10):2221-32
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Identification of a functionally essential amino acid for Arabidopsis cyclic nucleotide gated ion channels using the chimeric AtCNGC11/12 gene.Baxter J, Moeder W, Urquhart W, Shahinas D, Chin K, Christendat D, Kang HG, Angelova M, Kato N, Yoshioka K.Plant J. 2008 Nov;56(3):457-69
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Structural insight on the mechanism of regulation of the MarR family of proteins: high-resolution crystal structure of a transcriptional repressor from Methanobacterium thermoautotrophicum.Saridakis V, Shahinas D, Xu X, Christendat D.J. Mol. Biol. 2008 Mar;377(3):655-67
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2006

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Structure of Arabidopsis dehydroquinate dehydratase-shikimate dehydrogenase and implications for metabolic channeling in the shikimate pathway.Singh SA, Christendat D.Biochemistry 2006 Jun;45(25):7787-96
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Biochemical characterization of prephenate dehydrogenase from the hyperthermophilic bacterium Aquifex aeolicus.Bonvin J, Aponte RA, Marcantonio M, Singh S, Christendat D, Turnbull JL.Protein Sci. 2006 Jun;15(6):1417-32
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Crystal structure of prephenate dehydrogenase from Aquifex aeolicus. Insights into the catalytic mechanism.Sun W, Singh S, Zhang R, Turnbull JL, Christendat D.J. Biol. Chem. 2006 May;281(18):12919-28
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2005

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The crystal structure of a novel SAM-dependent methyltransferase PH1915 from Pyrococcus horikoshii.Sun W, Xu X, Pavlova M, Edwards AM, Joachimiak A, Savchenko A, Christendat D.Protein Sci. 2005 Dec;14(12):3121-8
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Crystal structure of a novel shikimate dehydrogenase from Haemophilus influenzae.Singh S, Korolev S, Koroleva O, Zarembinski T, Collart F, Joachimiak A, Christendat D.J. Biol. Chem. 2005 Apr;280(17):17101-8
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2004

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Crystal structure of the hypothetical protein TA1238 from Thermoplasma acidophilum: a new type of helical super-bundle.Sanishvili R, Pennycooke M, Gu J, Xu X, Joachimiak A, Edwards AM, Christendat D.J. Struct. Funct. Genomics 2004;5(4):231-40
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The structural basis for methylmalonic aciduria. The crystal structure of archaeal ATP:cobalamin adenosyltransferase.Saridakis V, Yakunin A, Xu X, Anandakumar P, Pennycooke M, Gu J, Cheung F, Lew JM, Sanishvili R, Joachimiak A, Arrowsmith CH, Christendat D, Edwards AM.J. Biol. Chem. 2004 May;279(22):23646-53
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Crystal structure of chorismate synthase from Aquifex aeolicus reveals a novel beta alpha beta sandwich topology.Viola CM, Saridakis V, Christendat D.Proteins 2004 Jan;54(1):166-9
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Structure- and function-based characterization of a new phosphoglycolate phosphatase from Thermoplasma acidophilum.Kim Y, Yakunin AF, Kuznetsova E, Xu X, Pennycooke M, Gu J, Cheung F, Proudfoot M, Arrowsmith CH, Joachimiak A, Edwards AM, Christendat D.J. Biol. Chem. 2004 Jan;279(1):517-26
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2003

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Crystal structures of MTH1187 and its yeast ortholog YBL001c.Tao X, Khayat R, Christendat D, Savchenko A, Xu X, Goldsmith-Fischman S, Honig B, Edwards A, Arrowsmith CH, Tong L.Proteins 2003 Aug;52(3):478-80
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Data mining crystallization databases: knowledge-based approaches to optimize protein crystal screens.Kimber MS, Vallee F, Houston S, Necakov A, Skarina T, Evdokimova E, Beasley S, Christendat D, Savchenko A, Arrowsmith CH, Vedadi M, Gerstein M, Edwards AM.Proteins 2003 Jun;51(4):562-8
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Structural proteomics: toward high-throughput structural biology as a tool in functional genomics.Yee A, Pardee K, Christendat D, Savchenko A, Edwards AM, Arrowsmith CH.Acc. Chem. Res. 2003 Mar;36(3):183-9
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Deep trefoil knot implicated in RNA binding found in an archaebacterial protein.Zarembinski TI, Kim Y, Peterson K, Christendat D, Dharamsi A, Arrowsmith CH, Edwards AM, Joachimiak A.Proteins 2003 Feb;50(2):177-83
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2002

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The crystal structure of MT0146/CbiT suggests that the putative precorrin-8w decarboxylase is a methyltransferase.Keller JP, Smith PM, Benach J, Christendat D, deTitta GT, Hunt JF.Structure 2002 Nov;10(11):1475-87
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Crystal structure of MTH169, a crucial component of phosphoribosylformylglycinamidine synthetase.Batra R, Christendat D, Edwards A, Arrowsmith C, Tong L.Proteins 2002 Nov;49(2):285-8
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The crystal structure of hypothetical protein MTH1491 from Methanobacterium thermoautotrophicum.Christendat D, Saridakis V, Kim Y, Kumar PA, Xu X, Semesi A, Joachimiak A, Arrowsmith CH, Edwards AM.Protein Sci. 2002 Jun;11(6):1409-14
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Crystal structure of Methanobacterium thermoautotrophicum conserved protein MTH1020 reveals an NTN-hydrolase fold.Saridakis V, Christendat D, Thygesen A, Arrowsmith CH, Edwards AM, Pai EF.Proteins 2002 Jul;48(1):141-3
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