Furey Lab

The Furey lab concentrates on the following:

1) Determination and analysis of structure-function relationships in macromolecules of biological interest, including thiamin diphosphate dependent enzymes, immunoglobulins, bacterial toxins, digestive enzymes and other proteins. X-Ray Crystallography is the primary method employed.

2) Development of techniques for the determination and analysis of macromolecular crystal structures.

3) Application /development of computing techniques and algorithms for understanding biological function on a molecular level.

 

Palaniappa Arjunan, PhD
Research Instructor


Matthew J. Whitley, PhD
Research Instructor

Palaniappa Arjunan, PhD

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.

William Furey, PhD

Koharudin L, W Furey and A Gronenborn.  Novel fold and carbohydrate specificity of the potent anti-HIV cyanobacterial lectin from oscillatoria agardhii.  J Biol Chem 286:1588-1597, 2011.
Matei E, A Zheng, W Furey, J Rose, C Aiken and A Gronenborn.  Anti-HIV activity of defective cyanovirin-N mutants is restored by dimerization.  J Biol Chem 285:13057-13065, 2010.
Nemeria N, P Arjunan, K Chandrasekhar, M Mossad, K Tittmann, W Furey and F Jordan.  Communication beween thiamin cofactors in the Escherichia coli pyruvate dehydrogenase complex E1 component active center:  Evidence for a "direct pathway" between the 4'-aminopyridine N1' atoms.  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 Cat B:  Enzymatic 61:14-22, 2009.
Kale S, G Ulas, J Song, G Brudvig, W Furey and F Jordan. Efficient coupling of catalysis and dynamics in the E1 component of escherichia coli pyruvate dehydrogenase multienzyme complex. Proc Natl Acad Sci 105(4):1158-1163, 2008.
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.
Jordan F, N Nemeria, S Zhang, Y Yan, P Arjunan and W Furey. Dual catalytic apparatus of the thiamin diphosphate coenzyme: Acid-base via the 1’.4’ iminopyrimidine tautomer along with its electrophilic role. J Am Chem Soc 125:12732-12738, 2003.
Nemeria N, P Arjunan, A Brunskill, F Sheibani, W Wei, Y Yan, S Zhang, F Jordan and W Furey. Histidine 407, a phantom residue in the E1 subunit of the Escherichia coli pyruvate dehydrogenase complex, activates reductive acetylation of lipoamide on the E2 subunit. An explanation for conservation of active sites between the E1 subunit and transketolase. Biochemistry 41(52):15459-15467, 2002.
Arjunan P, N Nemeria, A Brunskill, K Chandrasekhar, M Sax, Y Yan, F Jordan, J Guest and W Furey. Structure of the pyruvate dehydrogenase multienzyme complex E1 component from Escherichia coli at 1.85Å resolution. Biochemistry 41(16):5213-5221, 2002.
Furey W and S Swaminathan. PHASES-95: A Program Package for Processing and Analysing Diffraction Data From Macromolecules in Methods in Enzymology: Macromolecular Crystallography, Part B, Vol 277, eds. C. Carter & R. Sweet, Academic Press, Orlando, Fl., pp 590-620, 1997.

Matthew J. Whitley, PhD

Whitley MJ, Arjunan P, Nemeria NS, Korotchkina LG, Park YH, Patel MS, Jordan F and Furey W.  Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the alphaV138M variant of human pyruvate dehydrogenase. J Biol Chem. 293: 13204-13213, 2018.
Boatz JC, Whitley MJ, Li M, Gronenborn AM and van der Wel PCA. Cataract-associated P23T γD-crystallin retains a native-like fold in amorphous-looking aggregates formed at physiological pH. Nat Commun. 8:15137, 2017.
Whitley MJ, Xi Z, Bartko JC, Jensen MR, Blackledge M and Gronenborn AM. A combined NMR and SAXS analysis of the partially folded cataract-associated V75D γD-Crystallin. Biophys J. 12:1135-114, 2017.
Xi Z, Whitley MJ and Gronenborn AM. Human βB2-Crystallin forms a face-en-face dimer in solution: An integrated NMR and SAXS study. Structure 25:496-505, 2017.
 
McDonald LR, Whitley MJ, Boyer JA and Lee AL. Colocalization of fast and slow timescale dynamics in the allosteric signaling protein CheY. J Mol Biol. 425:2372-2381, 2013.
Whitley MJ, Furey W, Kollipara S and Gronenborn AM. Burkholderia oklahomensis agglutinin is a canonical two-domain OAA-family lectin: structures, carbohydrate  binding and anti-HIV activity. FEBS J. 280:2056-2067, 2013.
Whitley MJ and Lee AL. Exploring the role of structure and dynamics in the function of chymotrypsin inhibitor 2. Proteins 79:916-924, 2011.
 
Whitley MJ and Lee AL. Frameworks for understanding long-range intra-protein communication. Curr Protein Pept Sci. 10:116-127, 2009.