Prof Snezana Djordjevic

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Personal Profile

Name: Snezana Djordjevic Email: s.djordjevic@ucl.ac.uk
Title: Prof Tel: 020 7679 2230
Department: Structural & Molecular Biology Fax:
Position: Professor of Structural Biology of Signalling Address: Darwin Bldg., Gower Street, London, WC1E 6BT
Research Domain: Basic Life Sciences, Cardiometabolic Science, Personalised Medicine Web Page:  

Profile

Research Description

My research always included multitude of different techniques such as enzymatic studies, ITC and UV/VIS spectroscopy, molecular modelling, and site-directed mutagenesis that complemented X-ray crystallographic analysis of the proteins of interest. Following my PhD, I worked as a Howard Hughes Medical Institute research associate in the laboratory of Ann Stock that was investigating bacterial signal transduction proteins regulating bacterial chemotaxis. I solved crystal structures of receptor methyltransferase, methylesterase and methyltransferase in complex with the C-terminal receptor peptide. In 1998 I moved to UK and after a short career break I spent a year as a post-doctoral research scientist at MRC-LMB. Since 2000 I am at UCL where, capitalizing on my experience in methylation/demethylation regulation of bacterial chemotaxis receptors I developed a research in methylation regulation of eukaryotic signal-transduction protein + protein phosphatase PP2A. At the same time as a result of collaborations with Prof Ortiz de Montellano from UCSF and Prof Kelly and Dr Wilkinson from London School of Hygiene & Tropical Medicine, I have developed research in molecular basis of various pathogens oxidative stress defense mechanisms. We have solved a crystal structure of wild type and several catalytic-site specific mutants of AhpD from M. tuberculosis. This enzyme with unique folding topology and thioredoxin-like activity supports AhpC catalyzed reduction of ROSs in Mtb. In conjunction with this project we are also studying unique peroxidases from T. cruzi, and we have recently solved a crystal structure of GPXI from this organism.


Currently my laboratory is engaged in both basic and translational research involving signalling in prokaryotes and human systems.   We instigated structural, mechanistic and comparative genomics, investigations of two-component regulatory systems in M. Tuberculosis and, in collaboration with Dr J. Santini, NT-26 - an arsenite utilising bacterium.  At the same time, through industrial and academic collaborations, we are engaged in providing structural and biophysical support for the specific drug-discovery programmes targeting human transmembrane receptors implicated in cancer and cardiovascular diseases. 

Research Activities

Drug discovery

Molecular basis of enzyme mechanisms

Signal-transduction

Education Description

Course organizer for BIOC2004 Biomolecular Structure and Function course. Liaison tutor for Human Sciences degree programme.

UCL Collaborators

External Collaborators

Publications

    2014

    • Moyes A, Khambata R, Villar I, Bubb K, Baliga R, Lumsden N, Xiao F, Gane P, Rebstock A-S, Worthington R, Simone M, Quinteiro F, Rivilla F, Vallejo S, Peiro C, Sanchez-Ferrer CF, Djordjevic S, Caulfield M, MacAllister R, Ahluwalia A, Selwood D, Hobbs A (2014). Endothelial C-type natriuretic peptide maintains vascular homeostasis. The Journal of Clinical Investigation, , - .
    • Aqil R, Jia H, Cheng L, Shaikh S, Jarvis A, Chapman C, Chan AWE, Hartzoulakis B, Evans IM, Frolov A, Frankel P, Djordjevic S, Zachary IC, Selwood DL (2014). N-terminal modification of VEGF-A C-terminus derived peptides delineates structural features involved in neuropilin-1 binding and functional activity. ChemBioChem: a European journal of chemical biology, , - .

    2013

    • Wojnowska M, Yan J, Sivalingam G, Cryar A, Gor J, Thalassinos K, Djordjevic S (2013). Autophosphorylation activity of a soluble hexameric histidine kinase correlates with the shift in protein conformational equilibrium. Chemistry & Biology, , - . doi:10.1016/j.chembiol.2013.09.008
    • Seyedarabi A, Cheng L, Zachary I, Djordjevic S (2013). Production of soluble human vascular endothelial growth factor VEGF-A165-heparin binding domain in Escherichia coli.. PLoS One, 8(2), e55690 - . doi:10.1371/journal.pone.0055690
    • Djordjevic S, Driscoll PC (2013). Targeting VEGF signalling via the neuropilin co-receptor.. Drug Discov Today, 18(9-10), 447 - 455. doi:10.1016/j.drudis.2012.11.013

    2012

    • Wojnowska M, Djordjevic S (2012). Arsenite oxidation - regulation of gene expression. In Santini JM, Ward SA (Ed.), The Metabolism of Arsenite (pp. 115 - 124). : CRC Press.

    2011

    • Quinteiro FM, Gane P, Rebstock A-S, Worthington R, Simone M, Djordjevic S, Hobbs A, Selwood D (2011). Design and development of novel non-peptide agonists at NPR-C. doi:10.1186/1471-2210-11-S1-P54
    • Djordjevic S, Allerston CK, Jarvis A, Jia HY, Herzog B, Garza-Garcia A, Driscoll PC, Zachary I, Selwood D (2011). Small molecule inhibitors of the neuropilin-1 VEGF-A interaction.
    • Tsai ML, Cronin N, Djordjevic S (2011). The structure of human leucine carboxyl methyltransferase 1 that regulates protein phosphatase PP2A.. Acta Crystallogr D Biol Crystallogr, 67(Pt 1), 14 - 24. doi:10.1107/S0907444910042204

    2010

    • Patel S, Hussain S, Harris R, Sardiwal S, Kelly JM, Wilkinson SR, Driscoll PC, Djordjevic S (2010). Structural insights into the catalytic mechanism of Trypanosoma cruzi GPXI (glutathione peroxidase-like enzyme I).. Biochem J, 425(3), 513 - 522. doi:10.1042/BJ20091167
    • Sardiwal S, Santini JM, Osborne TH, Djordjevic S (2010). Characterization of a two-component signal transduction system that controls arsenite oxidation in the chemolithoautotroph NT-26. FEMS Microbiol Lett, , - . doi:10.1111/j.1574-6968.2010.02121.x
    • Jarvis A, Allerston CK, Jia H, Herzog B, Garza-Garcia A, Winfield N, Ellard K, Aqil R, Lynch R, Chapman C, Hartzoulakis B, Nally J, Stewart M, Cheng L, Menon M, Tickner M, Djordjevic S, Driscoll PC, Zachary I, Selwood DL (2010). Small molecule inhibitors of the neuropilin-1 vascular endothelial growth factor A (VEGF-A) interaction.. J Med Chem, 53(5), 2215 - 2226. doi:10.1021/jm901755g
    • Djordjevic S, Zhang X, Bartlam M, Ye S, Rao Z, Danpure CJ (2010). Structural implications of a G170R mutation of alanine:glyoxylate aminotransferase that is associated with peroxisome-to-mitochondrion mistargeting.. Acta Crystallogr Sect F Struct Biol Cryst Commun, 66(Pt 3), 233 - 236. doi:10.1107/S1744309109054645

    2008

    • Djordjevic S, Barrett T, Pitts J, Slingsby C, Moss D, Sansom C, Keep N (2008). The web-based teaching in the Institute of Structural and Molecular Biology, University of London. Acta Cryst., A64, C80 - C80.
    • Parkinson GN, Vines D, Driscoll PC, Djordjevic S (2008). Crystal structures of PI3K-C2alpha PX domain indicate conformational change associated with ligand binding.. BMC Structural Biology, 8(13), - . doi:10.1186/1472-6807-8-13
    • Djordjevic S (2008). X-ray crystallography and NMR spectroscopy in unravelling the catalytic mechanism of a peroxiredoxin. Acta Cryst., A64, C461 - C461.

    2005

    • Sardiwal S, Kendall SL, Movahedzadeh F, Rison SC, Stoker NG, Djordjevic S (2005). A GAF domain in the hypoxia/NO-inducible Mycobacterium tuberculosis DosS protein binds haem.. Journal of Molecular Biology, 353(5), 929 - 936. doi:10.1016/j.jmb.2005.09.011
    • Nunn CM, Jeeves M, Cliff MJ, Urquhart GT, George RR, Chao LH, Tscuchia Y, Djordjevic S (2005). Crystal structure of tobacco etch virus protease shows the protein C terminus bound within the active site.. J Mol Biol, 350(1), 145 - 155. doi:10.1016/j.jmb.2005.04.013

    2004

    • Perez E, West AH, Stock AM, Djordjevic S (2004). Discrimination between different methylation states of chemotaxis receptor Tar by receptor methyltransferase CheR.. Biochemistry, 43(4), 953 - 961. doi:10.1021/bi035455q

    2003

    • Koshkin A, Nunn CM, Djordjevic S, Ortiz de Montellano PR (2003). The mechanism of Mycobacterium tuberculosis alkylhydroperoxidase AhpD as defined by mutagenesis, crystallography, and kinetics. Journal of Biological Chemistry, 278(32), 29502 - 29508. doi:10.1074/jbc.M303747200

    2002

    • Nunn CM, Djordjevic S, Hillas PJ, Nishida CR, Ortiz de Montellano PR (2002). The crystal structure of Mycobacterium tuberculosis alkylhydroperoxidase AhpD, a potential target for antitubercular drug design. Journal of Biological Chemistry, 277(22), 20033 - 20040.
    • George RR, Harris R, Nunn CM, Cramer R, Djordjevic S (2002). Chaperonin assisted overexpression, purification and characterisation of human PP2A methyltransferase. Protein Expression and Purification, 26, 266 - 274.
    • Djordjevic S, Driscoll PC (2002). Structural insight into substrate and regulatory mechanisms of phosphoinositide 3-kinases. Trends in Biochemical Sciences, 27(8), 426 - 432.

    2001

    • Stock AM, Anand G, Djordjevic S, Goudreau P, West AH (2001). Response regulators and receptor modification enzymes involved in bacterial chemotaxis.. BIOPHYS J, 80(1), 172A - 172A.

    2000

    • (2000). The crystal structure of yeast phenylalanine tRNA at 2 A resolution: cleavage by Mg2+ in 15 year old crystals. Journal of Molecular Biology, 301, 401 - 414.

    1999

    • Djordjevic S, Stock AM, Chen Y, Stock J (1999). Protein methyltransferases involved in signal trandsuction. In Cheng X, Blumenthal RM (Ed.), Structure and Function of AdoMet-Dependent Methyltransferases (pp. 149 - 183). : World Scientific Publishing Co. Pte. Ltd..

    1998

    • Djordjevic S, Goudreau PN, Xu Q, Stock AM, West AH (1998). Structural basis for methylesterase CheB regulation by a phosphorylation-activated domain.. Proc Natl Acad Sci U S A, 95(4), 1381 - 1386.
    • Djordjevic S, Stock AM (1998). Structural analysis of bacterial chemotaxis proteins: components of a dynamic signaling system.. J Struct Biol, 124(2-3), 189 - 200. doi:10.1006/jsbi.1998.4034
    • Djordjevic S, Stock AM (1998). Chemotaxis receptor recognition by protein methyltransferase CheR.. Nat Struct Biol, 5(6), 446 - 450.

    1997

    • Djordjevic S, Stock AM (1997). Crystal structure of the chemotaxis receptor methyltransferase CheR suggests a conserved structural motif for binding S-adenosylmethionine.. Structure, 5(4), 545 - 558.

    1996

    • Djordjevic S, Stock A (1996). Crystal structure of CheR, bacterial chemotaxis receptor methyltransferase. Acta Cryst., A52, C187 - C187.
    • Kim JJ, Roberts DL, Djordjevic S, Wang M, Shea TM, Masters BS (1996). Crystallization studies of NADPH-cytochrome P450 reductase.. Methods Enzymol, 272, 368 - 377.

    1995

    • West AH, Djordjevic S, Martinez-Hackert E, Stock AM (1995). Purification, crystallization, and preliminary X-ray diffraction analyses of the bacterial chemotaxis receptor modifying enzymes.. Proteins, 21(4), 345 - 350. doi:10.1002/prot.340210407
    • Djordjevic S, Pace CP, Stankovich MT, Kim JJ (1995). Three-dimensional structure of butyryl-CoA dehydrogenase from Megasphaera elsdenii.. Biochemistry, 34(7), 2163 - 2171.
    • Djordjevic S, Roberts DL, Wang M, Shea T, Camitta MG, Masters BS, Kim JJ (1995). Crystallization and preliminary x-ray studies of NADPH-cytochrome P450 reductase.. Proc Natl Acad Sci U S A, 92(8), 3214 - 3218.

    1994

    • Kim JJP, Wang M, Djordjevic S, Paschke R, Bennett DW, Vockley J (1994). Three dimensional structures of acyl-CoA dehydrogenases: Structural basis of substrate specificity.
    • Djordjevic S, Dong Y, Paschke R, Frerman FE, Strauss AW, Kim JJ (1994). Identification of the catalytic base in long chain acyl-CoA dehydrogenase.. Biochemistry, 33(14), 4258 - 4264.
    • DJORDJEVIC S, WANG M, SHEA T, ROBERTS D, CAMITTA M, MASTERS BSS, KIM JJP (1994). CRYSTALLIZATION AND PRELIMINARY-X-RAY STUDIES OF NADPH-CYTOCHROME-P-450 REDUCTASE. FASEB J, 8(7), A1244 - A1244.

    1992

    • Kim JJ, Wang M, Djordjevic S, Paschke R (1992). The three dimensional structure of acyl-CoA dehydrogenases.. Prog Clin Biol Res, 375, 111 - 126.
    • CAMITTA M, NARAYANASAMI R, DJORDJEVIC S, HOROWITZ PM, ALEXANDER LM, MASTERS BSS (1992). STRUCTURE-FUNCTION STUDIES ON FAD-FREE AND FMN-FREE NADPH-CYTOCHROME P450 REDUCTASE USING FLUORESCENCE SPECTROSCOPY. FASEB J, 6(5), A1845 - A1845.

    1991

    • MCCABE TJ, CLARK JE, DJORDJEVIC S, MASTERS BS (1991). HORMONAL INDUCTION OF CYTOCHROME-P450 MEDIATED OMEGA-HYDROXYLATION OF EICOSANOIDS IN RABBIT LUNG AND KIDNEY. FASEB J, 5(6), A1518 - A1518.