Crystal structure of bovine 3-hydroxyanthranilate 3,4-dioxygenase.
3-Hydroxyanthranilate 3,4-dioxygenase, the enzyme that catalyzes the conversion of 3-hydroxyanthranilate to quinolinic acid, has been extracted and purified from bovine kidney, crystallized and its structure determined at 2.5 A resolution. The enzyme, which crystallizes in the triclinic P1 space group, is a monomer, characterized by the so-called cupin fold. The monomer of the bovine enzyme mimics the dimer present in lower species, such as bacteria and yeast, since it is composed of two domains: one of them is equivalent to one monomer, whilst the second domain corresponds to only a portion of it. The active site consists of an iron ion coordinated by two histidine residues, one glutamate and an external ligand, which has been interpreted as a solvent molecule. It is contained in the N-terminal domain, whilst the function of the C-terminal domain is possibly structural. The catalytic mechanism very likely has been conserved through all species, since the positions of all residues considered relevant for the reaction are present from bacteria to humans.
Dilović
Ivica
I
Department of Chemistry, University of Zagreb, Horvatovac 102a, Zagreb 10000, Croatia.
Gliubich
Francesca
F
Malpeli
Giorgio
G
Zanotti
Giuseppe
G
Matković-Calogović
Dubravka
D
D050561:3-Hydroxyanthranilate 3,4-Dioxygenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015095:3-Hydroxyanthranilic Acid / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D002417:Cattle; D003460:Crystallization; D018360:Crystallography, X-Ray; D018698:Glutamic Acid / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D007501:Iron / Q000737:chemistry; D007668:Kidney / Q000201:enzymology; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017378:Quinolinic Acid / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D015095:3-Hydroxyanthranilic Acid; D018698:Glutamic Acid; D006639:Histidine; D007501:Iron; D050561:3-Hydroxyanthranilate 3,4-Dioxygenase; D017378:Quinolinic Acid