Structural Details in the beta-elimination Mechanism of Tyrosine Phenol-lyase (CROSBI ID 529309)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa
Podaci o odgovornosti
Milić, Dalibor ; Matković-Čalogović, Dubravka ; Demidkina, Tatyana V. ; Antson, Alfred A.
engleski
Structural Details in the beta-elimination Mechanism of Tyrosine Phenol-lyase
Tyrosine phenol-lyase (TPL ; EC 4.1.99.2) is a homotetrameric pyridoxal-5’ -phosphate (PLP)-dependent enzyme that catalyses the β -elimination of L-tyrosine (the reversible hydrolytic cleavage of L-tyrosine to phenol and ammonium pyruvate [1]). The β -elimination proceeds via several intermediate steps, including the cleavage of the Cβ – Cγ bond. In order to reveal details in the enzymatic reaction and understand structural events during the catalysis, we determined the X-ray structures of several different forms of TPL from Citrobacter freundii. All of them are the structures of non-covalent complexes which resemble the quinonoid or the aminoacrylate reaction intermediate. As previously shown [2], the TPL active site can possess two different conformations: open and closed. Our study showed that the proposed closure of the active site during the enzymatic reaction “ forces” the quinonoid intermediate into the “ strained” conformation, which resembles the transition structure, and thus makes the cleavage of the Cβ – Cγ bond easier. The “ strained” conformation of the quinonoid intermediate is stabilised by hydrogen bonding and van der Waals interactions with the active site residues. [1] Phillips, R.S. ; Demidkina, T.V. ; Faleev N.G. Biochim. Biophys. Acta, 2003, 1647, 167. [2] Milić, D. ; Matković-Čalogović, D. ; Demidkina, T.V. ; Kulikova, V.V. ; Sinitzina, N.I. ; Antson, A.A. Biochemistry, 2006, 45, 7544.
tyrosine phenol-lyase; protein-ligand complexes; enzyme mechanisms
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
Podaci o prilogu
2007.
objavljeno
Podaci o matičnoj publikaciji
Podaci o skupu
24th European Crystallographic Meeting
poster
22.08.2007-27.08.2007
Marrakesh, Maroko