Maria-Eirini Pandelia

Maria-Eirini Pandelia, Assistant Professor of BiochemistryAssistant Professor of Biochemistry

Research Description

Mapping the functional repertoire of (bio)inorganic systems and protein metallocofactors; paradigms of (bio)catalysts relevant to the human health and environment.

My research interests lie in the strong interplay between (bio)chemistry/(bio)catalysis, spectroscopy and kinetics, with particular focus on the dissection of the mechanistic determinants underlying medically and environmentally relevant enzymatic processes. My research relies on the synteny of bioinformatic, spectroscopic, structural and kinetic methods to identify and establish the modus operandii of metal-containing enzymes and delineate their catalytic and functional repertoire.

Correlation between sequence, structure and function

Establishing the operant mechanisms according to which (bio)catalysis takes place, consists of identifying the reactive species carrying out the ‘difficult’ chemistry. Because the enzymes that we are interested in not only play a key role in metabolic functions but also in industrially relevant applications, understanding their reactivity will allow us to direct and control these reactions. In most of the cases however the enzyme’s state that is responsible for catalysis is fleeting and cannot be characterized using conventional methods such as X-Ray crystallography. These short-lived intermediates can be identified and characterized by a combination of kinetic and spectroscopic approaches.

Fe/S clusters and Fe-containing enzymes or bioinorganic synthetic compounds 

The main focuses of the research carried out comprise the use of Mössbauer and EPR spectroscopies coupled to time-resolved kinetics(optical) and redox potentiometry. In particular, 57Fe-Mössbauer plays a pivotal role among the many spectroscopic techniques that are routinely used to characterize Fe/S clusters and Fe-containing enzymes or bioinorganic synthetic compounds. Its strength lies in the fact that all chemically distinct 57Fe-labeled species in the sample are detected, irrespective of their oxidation and spin states. The Mössbauer spectrum is the weighted superposition of the individual subspectra of the various Fe sites contained in the sample and their relative areas are proportional to the relative concentration of the corresponding Fe species. For example, Fe/S clusters have unique Mössbauer-spectroscopic properties that allow for their identification and detailed characterization of their electronic and geometric structures.57Fe-Mössbauer spectroscopy when combined with Electron Paramagnetic Resonance (EPR) spectroscopy and analytical methods to determine the Fe:protein (synthetic compound) ratio represents the most rigorous method for establishing the types and stoichiometry of various Fe-containing cofactors.

Figure showing what the functional role of iron-sulfur clusters in proteins involved in DNA synthesis and repair is

My work is centered on delineating the mechanisms according to which metalloproteins involved in processes essential for life perform the activation of small (or larger) molecules, how the specific identity of the metals in the active sites allows their chemical diversion and selectivity and what the functional role of iron-sulfur clusters in proteins involved in DNA synthesis and repair is. The research of the group revolves around proteins that are candidates to be the targets of new antiviral factors and to mediate DNA modifications and other important chemical transformations. These proteins often belong to large structural superfamilies with apparently similar representatives that are carrying out radically different reactions. We want to understand those functions and the extant determinants that endow this chemical versatility.

The experimental and theoretical approaches entail: transient and steady state kinetic properties (activity, rates, substrate binding and inhibition), thermodynamic properties (reduction potentials) under (non)catalytic conditions, electronic and chemical properties by Mössbauer/EPR spectroscopy, computational (bioinformatics) and structural biology (X-Ray crystallography, XAS methods) methods.

UV/VIS spectroelectrochemistry of FeS clusters

Selected Publications

  • Dong M, Horitani M, Dzikovski B, Pandelia ME, Krebs C, Freed JH, Hoffman BM, Lin H. "Organometallic Complex Formed by an Unconventional Radical S-Adenosylmethionine Enzyme." J Am Chem Soc. 2016 Aug 10;138(31):9755-8.

  • Lanz ND, Lee KH, Horstmann AK, Pandelia ME, Cicchillo RM, Krebs C, Booker SJ (2016). "Characterization of Lipoyl Synthase from Mycobacterium tuberculosis."Biochemistry. 2016 Mar 8;55(9):1372-83.

  • Aussignargues C, Pandelia ME, Sutter M, Plegaria JS, Zarzycki J, Turmo A, Huang J, Ducat DC, Hegg EL, Gibney BR, Kerfeld CA (2016). "Structure and Function of a Bacterial Microcompartment Shell Protein Engineered to Bind a [4Fe-4S] Cluster." J Am Chem Soc. 2016 Apr 27;138(16):5262-70.

  • Cox N, Nalepa A, Pandelia ME, Lubitz W, Savitsky A (2015). "Pulse Double-Resonance EPR Techniques for the Study of Metallobiomolecules." Methods Enzymol. 2015;563:211-49.

  • Rajakovich LJ, Nørgaard H, Warui DM, Chang WC, Li N, Booker SJ, Krebs C, Bollinger JM Jr, Pandelia ME (2015). "Rapid Reduction of the Diferric-Peroxyhemiacetal Intermediate in Aldehyde-Deformylating Oxygenase by a Cyanobacterial Ferredoxin: Evidence for a Free-Radical Mechanism." J Am Chem Soc. 2015 Sep 16;137(36):11695-709.

  • Hadj-Saïd J, Pandelia ME, Léger C, Fourmond V, Dementin S (2015). "The Carbon Monoxide Dehydrogenase from Desulfovibrio vulgaris." Biochim Biophys Acta. 2015 Dec;1847(12):1574-83.

  • Zhao Y, Vargas-Barbosa NM, Strayer ME, McCool NS, Pandelia ME, Saunders TP, Swierk JR, Callejas JF, Jensen L, Mallouk TE (2015). "Understanding the effect of monomeric iridium(III/IV) aquo complexes on the photoelectrochemistry of IrOx.nH2O-catalyzed water-splitting systems." J Am Chem Soc. 2015 Jul 15;137(27):8749-57.

  • Pandelia ME, Lanz ND, Booker SJ, Krebs C (2015). "Mössbauer spectroscopy of Fe/S proteins." Biochim Biophys Acta. 2015 Jun;1853(6):1395-1405.

  • Warui DM, Pandelia ME, Rajakovich LJ, Krebs C, Bollinger JM Jr, Booker SJ (2015). "Efficient delivery of long-chain fatty aldehydes from the Nostoc punctiforme acyl-acyl carrier protein reductase to its cognate aldehyde-deformylating oxygenase." Biochemistry 2015 Feb 3;54(4):1006-15.

  • Lanz ND, Pandelia ME, Kakar ES, Lee KH, Krebs C, Booker SJ (2014). "Evidence for a catalytically and kinetically competent enzyme-substrate cross-linked intermediate in catalysis by lipoyl synthase."Biochemistry 2014, 53(28):4557-72.

  • Ludwig M, Pandelia ME, Chew CY, Zhang B, Golbeck JH, Krebs C, Bryant DA (2014). "ChlR protein of Synechococcus sp. PCC 7002 is a transcription activator that uses an oxygen-sensitive [4Fe-4S] cluster to control genes involved in pigment biosynthesis." J Biol Chem. 2014 Jun 13;289(24):16624-39.

  • Wörsdörfer B, Lingaraju M, Yennawar NH, Boal AK, Krebs C, Bollinger JM Jr, Pandelia ME (2013). "Organophosphonate-degrading PhnZ reveals an emerging family of HD domain mixed-valent diiron oxygenases." Proc. Natl. Acad. Sci. USA, 2013, 110(47):18874-9.

  • Pandelia ME, Bykov D, Izsak R, Infossi P, Giudici-Orticoni MT, Bill E, Neese F, Lubitz W (2013). "Reply to Mouesca et al.: Electronic structure of the proximal [4Fe-3S] cluster of O2-tolerant [NiFe] hydrogenases." Proc Natl Acad Sci USA. 2013 Jul 9;110(28):E2539.

  • Banci L, Ciofi-Baffoni S, Mikolajczyk M, Winkelmann J, Bill E, Pandelia ME (2013). "Human anamorsin binds [2Fe-2S] clusters with unique electronic properties." J. Biol. Inorg. Chem., 2013, 18,pp 883-893.

  • Kampa M, Pandelia ME, Lubitz W, van Gastel M, Neese F (2013). "A metal-metal bond in the light-induced state of [NiFe] hydrogenases with relevance to hydrogen evolution." J. Am. Chem. Soc., 2013, 135(10):3915-25.

  • Pandelia ME, Bykov D, Izsak R, Infossi P, Giudici-Orticoni MT, Bill E, Neese F, Lubitz W (2013). "Electronic structure of the unique [4Fe-3S] cluster in O2-tolerant hydrogenases characterized by 57Fe Mossbauer and EPR spectroscopy." J. Am. Chem. Soc. 2013 135(42):15801-12.

  • Dassama LM, Jiang W, Varano PT, Pandelia ME, Conner DA, Xie J, Bollinger JM Jr, Krebs C (2012). "Radical-translocation intermediates and hurdling of pathway defects in 'super-oxidized' (Mn(IV)/Fe(IV)) Chlamydia trachomatis ribonucleotide reductase." J. Am. Chem. Soc., 2012, 20498–20506.

  • Flores M, Okamura MY, Niklas J, Pandelia ME, Lubitz W (2012). "Pulse Q-band EPR and ENDOR spectroscopies of the photochemically generated monoprotonated benzosemiquinone radical in frozen alcoholic solution." J Phys Chem B, 2012 August 2, 116(30):8890-900.

  • Pandelia ME, Lubitz W, Nitschke W (2012). "Evolution and diversification of Group 1 [NiFe] hydrogenases. Is there a phylogenetic marker for O(2)-tolerance?" Biochim Biophys Acta, 2012, 1817(9):1565-75.

  • Pandelia ME, Infossi P, Stein M, Giudici-Orticoni MT, Lubitz W (2012). "Spectroscopic characterization of the key catalytic intermediate Ni-C in the O2-tolerant [NiFe] hydrogenase I from Aquifex aeolicus: evidence of a weakly bound hydride." Chem. Communications, 2012, 48, 823-825.

  • Hoppe A, Pandelia ME, Gärtner W, Lubitz W (2011). "[Fe4S4]- and [Fe3S4]-cluster formation in synthetic peptides." BBA-Bioenergetics 1807, 11,1414-1422.

  • Pandelia ME, Nitschke W, Infossi P, Giudici-Orticoni MT, Bill E, Lubitz W (2011). "Characterization of a unique [FeS] cluster in the electron transfer chain of the oxygen tolerant [NiFe] hydrogenase from Aquifex aeolicus." Proc. Nat. Acad. Sci. USA 2011 Apr 12; 108(15): 6097–6102.

  • Millo D, Hildebrandt P, Pandelia ME, Lubitz W, Zebger I (2011). "SEIRA spectroscopy of the electrochemical activation of an immobilized [NiFe] hydrogenase under turnover and non-turnover conditions." Ang. Chemie Int. Ed. 2011 Mar 7;50(11):2632-4.

  • Pandelia ME, Infossi P, Giudici-Orticoni MT, Lubitz W (2010). "The oxygen-tolerant hydrogenase I from Aquifex aeolicus weakly interacts with carbon monoxide: an electrochemical and time-resolved FTIR study." Biochemistry. 2010 Oct 19;49(41):8873-81.

  • Kellers P, Pandelia ME, Currell LJ, Görner H, Lubitz W (2009). "FTIR study on the light sensitivity of the [NiFe] hydrogenase from Desulfovibrio vulgaris Miyazaki F: Ni-C to Ni-L photoconversion, kinetics of proton rebinding and H/D isotope effect." Phys. Chem. Chem. Phys. 11: 8680 – 8683. *Equal authorship.

  • Pandelia ME, Fourmond V, Tron-Infossi P, Lojou E, Bertrand P, Léger C, Giudici-Orticoni MT, Lubitz W (2010). "Membrane-bound hydrogenase I from the hyperthermophilic bacterium Aquifex aeolicus: enzyme activation, redox intermediates and oxygen tolerance." J Am Chem Soc. 2010 May 26;132(20):6991-7004.