STRUCTURE OF THE ALDEHYDE OXIDO- REDUCTASE FROM DESULFOVIBRIO GIGAS: A MEMBER OF THE XANTHINE OXIDASE PROTEIN FAMILY. Archer, M.¹, Romco, M. J.^1,2 , Duarte, R.³ , Moura, I.³, Moura, J.J.G.³, LeGall, J.⁴, Hof, P.⁵, Huber, R.⁵, ¹ITQB, Apt 127, 2780 Oeiras, Portugal, ²IST, 1000 Lisboa, Portugal, ³FCT-UNL, 2785 Monte Caparica, Portugal, ⁴University of Georgia, Athens, GA 30602, USA, ⁵MPI, D-82152 Martinsried, Germany

The crystal structure of the Aldeyde Oxido-Reductase (MOP) has been solved by the MIR method at 2.25 Å resolution and refined to an Rfactor of 16.5% [1]. MOP, isolated from the sulfate reducing bacterium Desulfovibrio gigas is a homodimer of 907 aminoacid residues per subunit. It contains a molybdopterin co-factor (mo-co) and two different [2Fe-2S] centers and is folded into four domains. The first two bind the two iron sulfur clusters and the others are associated with Mo-co. Mo-co is a molybdopterin cytosine dinucleotide and is deeply buried in the protein and acessible through a 15 A deep tunnel. The Mo is penta-coordinated by two dithiolene sulfur atoms of the molybdopterin and three oxigen ligands. MOP oxidizes aldehydes to carboxilic acids. It belongs to an electron transfer chain, consisting of four proteins from D.gigas - flavodoxin, cytochrome c3 and hydrogenase - so that the oxidation of aldehydes may be linked to the generation of hydrogen. MOP sequence reveals homology to the xanthine oxidases. In xanthine oxidases (ca 1300 residues) the electron transfer occurs from the Mo site to a flavin group, which is absent in MOP. The crystal analysis of MOP shows the structure of Mo-co in detail and allows a first look at a member of the xanthine oxidase family. A structure-based catalytic mechanism for the xanthine oxidase family of molybdenum enzymes is proposed.

1. Romco, M. J., Archer, M., Moura, I., Moura, J. J. G., LeGall, J., Engh, R., Schneider, M., Hof, P., Huber, R. , Science 270, 1170 (1995).