Naslov
Structural investigations of bovine 3- hydroxyanthranilate 3, 4-dioxygenase

Autori
Đilović, Ivica

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, doktorska disertacija

Fakultet
Prirodoslovno-matematički fakultet

Mjesto
Zagreb

Datum
08.07

Godina
2011

Stranica
123

Mentor
Matković-Čalogović, Dubravka

Ključne riječi
dioxygenation / enzyme / protein crystallography / extradiol dioxygenase / cupin superfamily

Sažetak
3-Hydroxyanthranilate 3, 4-dioxygenase (3HAO) is responsible for the conversion of 3- hydroxyanthranilic acid (2-amino-3- hydroxybenzoic acid, 3HA) to quinolinic acid (2, 3-pyridinedicarboxylic acid, QUIN). It acts in the final step of the kynurenine pathway, where it catalyzes the opening of the benzene ring with the incorporation of both atoms of molecular oxygen. The enzyme is of special interest because the product of reaction which it catalyses is related with several neurogical disorders. For these reasons, the kynurenine pathway is considered to be a possible pharmacological target for such disorders. The bovine enzyme is a monomer consisting of 286 amino acids. Its crystal structure was determined at 2.5 Å resolution. The core motif is a jellyroll beta-barrel formed by two antiparallel beta -sheets with a topology which is characteristic of the cupin barrel fold. The iron-coordinating residues, two histidines and a glutamate, are highly conserved, as they are structurally similar to those found in other organisms. The pentacoordinated iron ion is in the active site and is bound deep inside the N- terminal cupin barrel. The enzyme 3HAO is an excellent example of the molecular evolution of a protein: from bacteria and simple eukaryotes, where it is a dimer, its structure has transformed in higher eukaryotes into a monomer that includes components of the dimer, suggesting that the mammalian enzyme could have originated by a gene-duplication event, followed by a divergent evolution.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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

POVEZANOST RADA