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Structural basis for the catalytic activity of tyrosine phenol-lyase (CROSBI ID 564086)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa

Milić, Dalibor ; Demidkina, Tatyana V. ; Matković-Čalogović, Dubravka ; Antson, Alfred A. Structural basis for the catalytic activity of tyrosine phenol-lyase // International School of Crystallography, 42nd Course, Structure and Function from Macromolecular Crystallography: Organisation in Space and Time - Programme, Lecture Notes & Poster Abstracts. 2010. str. 206-206

Podaci o odgovornosti

Milić, Dalibor ; Demidkina, Tatyana V. ; Matković-Čalogović, Dubravka ; Antson, Alfred A.

engleski

Structural basis for the catalytic activity of tyrosine phenol-lyase

Tyrosine phenol-lyase (TPL) is a pyridoxal-5'-phosphate (PLP)-dependent enzyme which catalyzes the reversible hydrolytic β-elimination reaction of L-tyrosine to produce phenol and ammonium pyruvate. In vitro, TPL also catalyzes some other reactions with different substrates. It is a homotetrameric protein with the active sites (one per subunit) located at the interface of two subunits forming the catalytic dimer [1]. Each protein subunit, and the corresponding active site, can adopt two different conformations: open and closed [2, 3]. The postulated mechanism of the physiological β-elimination reaction [4] includes several key steps: (a) formation of the external aldimine in the reaction of the internal aldimine with the substrate ; (b) Cα proton abstraction performed by the cofactor-binding residue Lys257 and resulting in formation of the quinonoid intermediate ; (c) Cγ protonation by Tyr71 assisted by Arg381 ; and, finally, (d) cleavage of the Cβ–Cγ bond to form phenol and the α-aminoacrylate intermediate which is decomposed to ammonium pyruvate. We have solved crystal structures of several complexes with substrate analogs. These structures mimic the reaction intermediates and suggest that closure of the active site is crucial for abstraction of phenol during the -elimination of L-tyrosine. The closure protects the key quinonoid intermediate from the solvent and brings the catalytically important residues Arg381, Thr124, and Phe448 into positions suitable for interaction with the substrate. 1. Antson, A. A., Demidkina, T. V., Gollnick, P., Dauter, Z., Von Tersch, R. L., Long, J., Berezhnoy, S. N., Phillips, R. S., Harutyunyan, E. H., and Wilson, K. S. (1993) Biochemistry 32, 4195–4206. 2. Milić, D., Matković-Čalogović, D., Demidkina, T. V., Kulikova, V. V., Sinitzina, N. I., and Antson, A. A. (2006) Biochemistry 45, 7544–7552. 3. Milić, D., Demidkina, T. V., Faleev, N. G., Matković-Čalogović, D., and Antson, A. A. (2008) J. Biol. Chem. 283, 29206–29214. 4. Phillips, R. S., Demidkina, T. V., and Faleev, N. G. (2003) Biochim. Biophys. Acta 1647, 167–172.

beta-elimination; enzyme; protein crystallography; pyridoxal 5'-phosphate; quinonoid; reaction mechanism; tyrosine phenol-lyase

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Podaci o prilogu

206-206.

2010.

objavljeno

Podaci o matičnoj publikaciji

International School of Crystallography, 42nd Course, Structure and Function from Macromolecular Crystallography: Organisation in Space and Time - Programme, Lecture Notes & Poster Abstracts

Podaci o skupu

International School of Crystallography, 42nd Course, Structure and Function from Macromolecular Crystallography: Organisation in Space and Time

poster

03.06.2010-13.06.2010

Erice, Italija

Povezanost rada

Kemija