Mechanistic, Structural and Inhibition Studies of Enzymes



Enzymes family that we are interested in from structural mechanistic and inhibition perspectives include serine proteases, oxygenases, crotonases (enolate forming enzymes), enzymes involved in the biosynthesis of flavonoids and the plant signaling molecule ethylene. Most of the enzymes that we work on are of bio/medicinal interest. However, we are especially interested in studying reactions that are unusual or challenging from a chemical perspective.




For representative publications see:

1.
Migaud ME, Wilmouth RC, Mills GI, Wayne GJ, Risley C, Chambers C, Macdonald SJF, Schofield CJ: 5,5-Fused Thiophene γ-Lactams as Templates for Serine Protease Inhibition. ChemInform 2002, 33: 130.
2.
Liu B, Schofield CJ, Wilmouth RC: Structural Analyses on Intermediates in Serine Protease Catalysis. Journal of Biological Chemistry 2006, 281: 24024 -24035.
3.
Katona G, Wilmouth RC, Wright PA, Berglund GI, Hajdu J, Neutze R, Schofield CJ: X-ray Structure of a Serine Protease Acyl-Enzyme Complex at 0.95-Å Resolution. Journal of Biological Chemistry 2002, 277: 21962 -21970.
4.
Wilmouth RC, Edman K, Neutze R, Wright PA, Clifton IJ, Schneider TR, Schofield CJ, Hajdu J: X-ray snapshots of serine protease catalysis reveal a tetrahedral intermediate. Nat. Struct. Biol 2001, 8: 689-694.
5.
Zhang Z, Ren J-S, Clifton IJ, Schofield CJ: Crystal Structure and Mechanistic Implications of 1-Aminocyclopropane-1-Carboxylic Acid Oxidase--The Ethylene-Forming Enzyme. Chemistry & Biology 2004, 11: 1383-1394.
6.
Turnbull JJ, Nakajima J-ichiro, Welford RWD, Yamazaki M, Saito K, Schofield CJ: Mechanistic Studies on Three 2-Oxoglutarate-dependent Oxygenases of Flavonoid Biosynthesis. Journal of Biological Chemistry 2004, 279: 1206 -1216.
7.
Clifton IJ, Hsueh L-C, Baldwin JE, Harlos K, Schofield CJ: Structure of proline 3-hydroxylase. European Journal of Biochemistry 2001, 268: 6625-6636.
8.
Wilmouth RC, Turnbull JJ, Welford RWD, Clifton IJ, Prescott AG, Schofield CJ: Structure and Mechanism of Anthocyanidin Synthase from Arabidopsis thaliana. Structure 2002, 10: 93-103.