Dr. Arjunan determines the structure of macromolecules of biological interest, and then analyses structure-function relationships. He primarily uses X-ray crystallography to accomplish this.

Dr. Arjunan's current research includes the high resolution three-dimensional structure determination of thiamin diphosphate(ThDP)-dependent enzymes, the yeast pyruvate decarboxylase (PDC) and pyruvate dehydrogenase multienzyme complex (PDHc) from Escherichia coli. The refined structure is then used to address long-standing issues regarding the structure and function of thiamin diphosphate-dependent enzymes. The structure determination also includes the structure of PDHc E1 in complex with a covalently bound reaction intermediate analogue. Other interests are: a) the crystal structural analysis of native and mutant ThDP-dependent enzymes, either alone or in complexes with substrates, inhibitors, activators or with other related enzymes and b) development of techniques for the determination and analysis of macromolecular crystal structure.

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Important Publications

Nemeria N, P Arjunan, K Chandrasekhar, M Mossad, K Tittmann, W Furey and F Jordan.  Communication between thiamin cofactors in the Escherichia coli pyruvate dehydrogenase complex E1 component active centers.  J Biol Chem 285:11197-11209, 2010.

Jordan F, P Arjunan, S Kale, N Nemeria and W Furey.  Multiple roles of mobile active center loops in the E1 component of the Escherichia coli pyruvate dehydrogenase complex:  Linkage of protein dynamics to catalysis.  J Mol Catal B:  Enzym 61:14-22, 2009.

Kale S, P Arjunan, W Furey and F Jorda. A dynamic loop at the active center of the Escherichia coli pyruvate dehydrogenase complex E1 component modulates substrate utilization and chemical communication with the E2 component, n. J Biol Chem 282:28106-28116, 2007.

Arjunan P, M Sax, A Brunskill, K Chandrasekhar, N Nemeria, S Zhang, F Jordan and W. Furey. A thiamin-bound, pre-decarboxylation reaction intermediate analogue in the pyruvate dehydrogenase E1 subunit induces large-scale disorder-to-order transformations in the enzyme and reveals novel structural features in the covalently bound adduct. J Biol Chem 281:15296-15303, 2006.

Nemeria N, K Tittmann, E Joseph. L Zhou, MB Vazquez-coll, P Arjunan, G Hubner, W Furey and F Jordan. Glutamate 636 of the Escherichia Coli Pyruvate dehydrogenase-E1 participates in active center communication and behaves as an engineered acetolactate synthase with unusual stereoselectivity. J Biol Chem 280:21473-21482, 2005.

Arjunan P, K Chandrasekhar, M Sax, A Brunskill, N Nemeria, F Jordan and W Furey. Structural determinants of enzyme binding affinity: The E1 component of pyruvate dehydrogenase from Escherichia coli in complex with the inhibitor thiamin thiazolone diphosphate. Biochemistry 43:2405-2411, 2004.

Jordan F, N Nemeria, Y Yan, S Zhang, P Arjunan and W Furey. Presence of the 1,4’-imino tautomer of thiamin diphosphate on the E1 subunit of the Escherichia coli pyruvate dehydrogenase complex provides evidence for an acid-base role, in addition to its long-accepted electrophilic role; A coenzyme with dual catalytic machinery. J Am Chem Soc 125:12732-12738, 2003.

Arjunan P, N Nemeria, A Brunskill, K Chandrasekhar, M Sax, Y Yan, F Jordan, JRGuest and W Furey. Structure of the pyruvate dehydrogenase multienzyme complex E1 component from Escherichia coli at 1.85 Å resolution., Biochemistry 41:5213-5221, 2002.