Professor Dinesh Christendat

Dinesh Christendat

Professor


Campus

St. George (downtown)

CSB Appointment

Full

Research Areas

Bioinformatics / Computational Biology, Metabolomics, Microbiology, Molecular Biology, Plant Biology, Structural Biology

Education

Ph.D. Concordia University

Primary Undergraduate Department

Cell & Systems Biology

Graduate Programs

Cell & Systems Biology

Academic or Administrative Appointments

Associate Chair for Undergraduate Studies

Research Description

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.


Contact Information

Office Phone: 416-946-8373
Office: ESC4052
Lab: ESC4045
Lab Phone: 416-946-8436
Email

Mailing Address

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

Visit lab’s website


Publications

2018

Structural and biochemical approaches uncover multiple evolutionary trajectories of plant quinate dehydrogenases.

Gritsunov A, Peek J, Diaz Caballero J, Guttman D, Christendat D
2018, The Plant journal : for cell and molecular biology, 29890023

Shikimate Induced Transcriptional Activation of Protocatechuate Biosynthesis Genes by QuiR, a LysR-Type Transcriptional Regulator, in Listeria monocytogenes.

Prezioso SM, Xue K, Leung N, Gray-Owen SD, Christendat D
2018, Journal of molecular biology, 430, 1265-1283, 29530613

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2016

Structurally diverse dehydroshikimate dehydratase variants participate in microbial quinate catabolism.

Peek J, Roman J, Moran GR, Christendat D
2017, Molecular microbiology, 103, 39-54, 27706847

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2014

Identification of Novel Polyphenolic Inhibitors of Shikimate Dehydrogenase (AroE)

Peek J, Shi T, Christendat D
2014, Journal of biomolecular screening, 19, 1090-1098, 24632659

The shikimate dehydrogenase family: functional diversity within a conserved structural and mechanistic framework.

Peek J, Christendat D
2015, Archives of biochemistry and biophysics, 566, 85-99, 25524738

Isolation and molecular characterization of the shikimate dehydrogenase domain from the Toxoplasma gondii AROM complex

Peek J, Castiglione G, Shi T, Christendat D
2014, Molecular and biochemical parasitology, 194, 16-9, 24731949

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2013

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
2013, The Plant journal : for cell and molecular biology, 76, 615-26, 24004165

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
2013, BMC genomics, 14, 162, 23496816

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2012

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
2013, Biochimica et biophysica acta, 1834, 516-23, 23142411

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2011

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
2011, Biochemistry, 50, 8616-27, 21846128

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
2011, Protein science : a publication of the Protein Society, 20, 1125-36, 21520319

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
2011, PloS one, 6, e15237, 21249219

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2009

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
2009, The Journal of biological chemistry, 284, 13223-32, 19279014

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2008

Evolutionary diversification of plant shikimate kinase gene duplicates

Fucile G, Falconer S, Christendat D
2008, PLoS genetics, 4, e1000292, 19057671

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
2008, The Plant journal : for cell and molecular biology, 56, 457-69, 18643993

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
2008, Molecular biology and evolution, 25, 2221-32, 18669580

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
2008, Journal of molecular biology, 377, 655-67, 18272181

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2006

Structure of Arabidopsis dehydroquinate dehydratase-shikimate dehydrogenase and implications for metabolic channeling in the shikimate pathway

Singh SA, Christendat D
2006, Biochemistry, 45, 7787-96, 16784230

Biochemical characterization of prephenate dehydrogenase from the hyperthermophilic bacterium Aquifex aeolicus

Bonvin J, Aponte RA, Marcantonio M, Singh S, Christendat D, Turnbull JL
2006, Protein science : a publication of the Protein Society, 15, 1417-32, 16731976

Crystal structure of prephenate dehydrogenase from Aquifex aeolicus. Insights into the catalytic mechanism

Sun W, Singh S, Zhang R, Turnbull JL, Christendat D
2006, The Journal of biological chemistry, 281, 12919-28, 16513644

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2005

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
2005, Protein science : a publication of the Protein Society, 14, 3121-8, 16260766

Crystal structure of a novel shikimate dehydrogenase from Haemophilus influenzae

Singh S, Korolev S, Koroleva O, Zarembinski T, Collart F, Joachimiak A, Christendat D
2005, The Journal of biological chemistry, 280, 17101-8, 15735308

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2004

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
2004, The Journal of biological chemistry, 279, 23646-53, 15044458

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
2004, Journal of structural and functional genomics, 5, 231-40, 15704011

Crystal structure of chorismate synthase from Aquifex aeolicus reveals a novel beta alpha beta sandwich topology

Viola CM, Saridakis V, Christendat D
2004, Proteins, 54, 166-9, 14705034

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2003

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
2004, The Journal of biological chemistry, 279, 517-26, 14555659

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
2003, Proteins, 52, 478-80, 12866058

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
2003, Proteins, 51, 562-8, 12784215

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
2003, Accounts of chemical research, 36, 183-9, 12641475

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
2003, Proteins, 50, 177-83, 12486711

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2002

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
2002, Structure (London, England : 1993), 10, 1475-87, 12429089

Crystal structure of MTH169, a crucial component of phosphoribosylformylglycinamidine synthetase

Batra R, Christendat D, Edwards A, Arrowsmith C, Tong L
2002, Proteins, 49, 285-8, 12211007

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
2002, Proteins, 48, 141-3, 12012346

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
2002, Protein science : a publication of the Protein Society, 11, 1409-14, 12021439

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