Venkatesan Research Group

Structural Biochemistry: Molecular Machines of Lipid Metabolism &Transport

Structural Biochemistry: Molecular machines of lipid metabolism & transport

Lipids are essential constituents of cells and an important source of energy and carbon in living organisms ranging from bacteria to human. A multitude of proteins and enzymes exist in the cell to facilitate the synthesis, transport and degradation of lipids.

Our group’s core interests are to understand the processes of lipid metabolism and lipid transport at a molecular level with a focus on multifunctional enzymes and multi-protein complexes using a variety of biophysical, biochemical and structural biological approaches.

Enzymes of the β-oxidation pathway from human, E. coli and mycobacteria

Fatty acids are degraded in iterative cycles of four steps. A number of enzymes are involved in the β-oxidation pathway with varying substrate specificities. Our aim is to understand the structural and functional properties of these enzymes, in particular, on the assembly, substrate specificity and substrate channeling properties of the trifunctional β-oxidation enzyme (TFE) complex. Our group has determined the structures of TFEs and their sub-units from M. tuberculosis (Mtb)and E. coli.

Mycobacterial mammalian-cell-entry (Mce) proteins

Mtb is one of the very few organisms which survives on the host lipids as a source of energy and carbon during the latent stage of infection. ABC transporters composed of the proteins encoded from the Mce1-4 operons are proposed to be involved in the transport of such lipids including cholesterol and fatty acids. Our group is working on these Mce-complexes to understand the assembly and lipid transport mechanism of these transporters.

 

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Research group members

Rajaram Venkatesan, Ph. D., Docent
Group Leader & Senior Research Fellow
 
Docent. Biochemistry, University of Oulu, Finland
Academy of Finland Research Fellow, University of Oulu, Finland
(Sep2015-Aug2020)
Ph.D. Structural Biology, Indian Institute of Science, Bangalore, India
M.Sc. Chemical Sciences, Pondicherry Central University, India
B.Sc. Chemistry, University of Madras, India
 
Email: rajaram.venkatesan (at) oulu.fi
Phone: +358 (0) 294 481185
Address: Room D76C, P.O.Box 5400, FIN-90014 University of Oulu, Finland

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Emeritus Professor
 
Professor. Biochemistry, University of Oulu
Ph.D. Research, State University Groningen, The Netherlands
M.Sc. Biochemistry, State University Groningen, The Netherlands
B.Sc. Chemistry, State University Groningen, The Netherlands
Email: rik.wierenga (at) oulu.fi
Phone: +358 (0) 29448 1199
Dhirendra Singh, Ph.D
Postdoctoral Researcher
 
Ph.D. Structural Biology, Nanyang Technical University, Singapore
M.Sc. Biochemistry, The Maharaja Sayajirao University of Baroda, India
B.Sc. Botany, The Maharaja Sayajirao University of Baroda, India
Email: dhirendra.singh (at) oulu.fi
Shruthi Sridhar, M.Sc.
Doctoral Student
 
Integrated M.Sc. Molecular Biology, University of Mysore, India
Email: shruthi.sridhar (at) oulu.fi
Subhadra Dalwani, M.Sc.
Doctoral Student
 
M.E. Biotechnology, BITS Pilani, India
B.E. Biotechnology, Visvesvaraya Technical University, India

Email: subhadra.dalwani (at) oulu.fi

Pooja, M.Sc.
Doctoral Student
 
M.Sc. Biotechnology, South Asian University, India
B.Sc. Biochemistry, University of Delhi, India

Email: pooja.pooja (at) oulu.fi

Mohammad Asadur Rahman, M. Sc.
Doctoral Student
 
M.Sc. Biochemistry and Molecular Biology, Huazhong Agricultural University, China
B.Sc. Genetic Engineering and Biotechnology, University of Rajshahi, Bangladesh

Email: asadur.rahman (at) oulu.fi

Ramita Sulu, M.Sc.
Doctoral Student
 
M.Sc. Protein Science and Biotechnology, University of Oulu, Finland
M.Sc. Microbiology, Tribhuvan University, Nepal

Email: ramita.sulu (at) oulu.fi

Mikko Hynönen, M.Sc.
Doctoral Student
 
M.Sc. Biochemistry, University of Oulu, Finland
B.Sc. Biochemistry, University of Oulu, Finland

Email: mikko.hynonen (at) oulu.fi

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Alumni

Shiv K. Sah-Teli, Ph.D.
Doctoral Student (2014-2020)
M.Sc. Protein Science and Biotechnology, University of Oulu, Finland
B.Sc. Biochemistry, Pokhara University, Nepal
 
Postdoctoral Researcher @ Prof Peppi Karppinen's group,
FBMM, University of Oulu, Finland
Email: shiv.sahteli (at) oulu.fi

Raphael Kunzmann
Visiting Laboratory Technician Trainee (Jul-Sep 2020)
 
 
 
Laboratory Technician @ Labor LS, BAD Bocklet, Germany

Email: raphael.kunzmann (at) labor-ls.de

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Selected Publications

  1. Sah-Teli S. K., Hynönen, M.J., Sulu, R., Dalwani, S., Schmitz, W., Wierenga, R.K., Venkatesan, R. Insights into the stability and substrate specificity of the E. coli aerobic β-oxidation trifunctional enzyme complex. J. Struct. Biol. 2020; 2010;3:107494 doi: 10.1016/j.jsb.2020.107494.
  2. Sah-Teli SK, Hynönen MJ, Schmitz W, Geraets JA, Seitsonen J, Pedersen JS, ButcherSJ, Wierenga RK, Venkatesan R. Complementary substrate specificity and distinct quaternary assembly of the Escherichia coli aerobic and anaerobic beta-oxidation trifunctional enzyme complexes. Biochem. J. 2019; 476: 1975-1994 doi: 10.1042/BCJ20190314
  3. Venkatesan R, Sah-Teli SK, Awoniyi LO, Jiang G, Prus P, Kastaniotis AJ, Hiltunen JK, Wierenga RK, Chen Z. Insights into mitochondrial fatty acid synthesis from the structure of heterotetrameric 3-ketoacyl-ACP reductase/3R-hydroxyacyl-CoA dehydrogenase. Nature Commun. 2014;5:4805. doi: 10.1038/ncomms5805
  4. Venkatesan R, Wierenga RK. Structure of mycobacterial β-oxidation trifunctional enzyme reveals its altered assembly and putative substrate channeling pathway. ACS Chemical Biology. 2013; 8:1063-1073
  5. Bisht S, Rajaram V, Bharath SR, Kalyani JN, Khan F, Rao AN, Savithri HS, Murthy MR. Crystal Structure of Escherichia coli diaminopropionate ammonia-lyase reveals mechanism of enzyme activation and catalysis. J Biol Chem. 2012; 287(24):20369-81
  6. Sharma S, Bhaumik P, Schmitz W, Venkatesan R, Hiltunen JK, Conzelmann E,Juffer AH, Wierenga RK. The enolization chemistry of a thioester-dependent racemase: the 1.4 Å crystal structure of a reaction intermediate complex characterized by detailed QM/MM calculations. J Phys Chem B. 2012; 116(11):3619-29
  7. Kasaragod P, Venkatesan R, Kiema TR, Hiltunen JK, Wierenga RK. Crystal structure of liganded rat peroxisomal multifunctional enzyme type 1: a flexiblemolecule with two interconnected active sites. J Biol Chem. 2010; 285(31):24089-28098.
  8. Wierenga RK, Kapetaniou EG, Venkatesan R. Triosephosphate isomerase: a highly evolved biocatalyst, Cellular and molecular life sciences. 2010; 67(23):3961-82.
  9. Chen Z, Kastaniotis AJ, Miinalainen IJ, Rajaram V, Wierenga RK, Hiltunen JK. 17beta-hydroxysteroid dehydrogenase type 8 and carbonyl reductase type 4 assemble as a ketoacyl reductase of human mitochondrial FAS. FASEB J. 2009; 23(11):3682-691.
  10. Vinitha RP,*Rajaram V,* Shveta Bisht, Bhavani BS, Appaji Rao N, Murthy MRN, Savithri HS. Structural and functional studies of Bacillus stearothermophilus serine hydroxymethyltransferase: the role of N341, Y60 and F351 in tetrahydrofolate binding, Biochem. J. 2009; 418:635–642
  11. Bhavani BS,* Rajaram V,* Shveta Bisht, Purnima Kaul, Prakash V, Murthy MRN, Appaji Rao N, Savithri HS. Importance of tyrosine residues of Bacillus stearothermophilus serine hydroxymethyltransferase in cofactor binding and L-allo-Thr cleavage: Crystal structure and biochemical studies, FEBS Journal. 2008;275: 4606–4619
  12. Rajaram V,* Bhavani BS*, Purnima Kaul, Prakash V, Appaji Rao N, Savithri, HS, Murthy MR. Structure determination and biochemical studies on Bacillus stearothermophilus E53Q Serine Hydroxymethyltransferase and its complexes provide insights on function and enzyme memory, FEBS Journal. 2007;274:4148-4160

 

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News & Events

Ph.D defence of M.Sc. Shiv K. Sah-Teli 

August 7, 2020 at 12:00 noon

@ Leena Palotie Lecture Hall

 

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Join us

Our group is working on the structural and biochemical aspects of multifunctional enzymes and protein complexes.

We are looking for enthusiastic and motivated pro-gradu students, graduate students and researchers to join us.

Contact Dr. Rajaram Venkatesan (rajaram.venkatesan@oulu.fi), if you are interested to know more about our projects and join us.

 

 

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Last updated: 25.9.2020