Naslov
Structural basis for the enzymatic activity of tyrosine phenol-lyase

Autori
Milić, Dalibor

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, doktorska disertacija

Fakultet
Prirodoslovno-matematički fakultet

Mjesto
Zagreb

Datum
02.06

Godina
2010

Stranica
161

Mentor
Matković-Čalogović, Dubravka ; Antson, Alfred A.

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

Sažetak
Tyrosine phenol-lyase (TPL) is a pyridoxal 5'-phosphate dependent enzyme which catalyzes the hydrolytic cleavage (beta-elimination) of L-tyrosine to phenol and ammonium pyruvate, and also many other chemical reactions with different natural and synthetic substrates. The beta-elimination reaction of L-tyrosine proceeds through several intermediate steps. In this work, the three-dimensional structures of several different forms of Citrobacter freundii TPL, including mutant proteins and complexes with ligands, were studied by the single-crystal X-ray diffraction analysis in a resolution range of 1.80-2.25 Å. The refined structures mimic the key intermediate steps in the reaction mechanism and provide a detailed view at the structural events during the enzymatic catalysis. The data indicate that a signicant conformational change of the protein subunit is crucial for the beta-elimination reaction. The catalytically important residues arginine-381 and threonine- 124 interact with the bound substrate only in the closed conformation of the active site. Structural data also show that phenylalanine-448 destabilizes the quinonoid intermediate.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

Napomena
Rad sadrži i "Prošireni sažetak" na hrvatskom jeziku.

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