ITQB’s research work highlighted on cover

The cover page of June 2008 issue from Acta Crystallographica Section D – Biological Crystallography presents a picture of the structure from the Desulfovibrio vulgaris hybrid Fe-S cluster protein (HCP). This structure was determined at the Macromolecular Crystallography Unit of ITQB by its former PhD student David Aragão (now a post-doc at Limerick University, Ireland) and co-workers.

In spite of various crystallographic structures, detailed spectroscopic analyses, and many other studies, the precise function(s) of HCPs is still subject to discussion. This study intended to compare the anaerobically purified form of the protein with other available structural forms, and to assess structural similarities between cluster proteins and carbon monoxide desydrogenases (CoDs).

The two protein families not only share similar folds but also contain similar clusters at equivalent positions, namely related Fe-S hybrid clusters at the interface of their three domains (in the centre of the picture), or canonical cubane Fe-S clusters near their N-terminal domains.  The clusters, although different, share striking similarities and are linked to the polypeptide chain via homologous ligands.

The HCP reaction mechanism may also be similar to the CoD reaction mechanism, with substrate binding to the top mobile part of the hybrid cluster followed by its reduction and release of an oxygen ion or hydroxyl group. Such a mechanism would fit both hydroxylamine reduction and hydrogen peroxide reduction as well as other small or linear substrates with the potential to be reduced.

In the light of current knowledge, the HCP substrate could be either a reactive nitrogen or oxygen species and further biochemical studies are needed to access and understand the true nature of the substrate of this enzyme in order to clarify its role in either protection against oxidative stress or reactive nitrogen stress.

David Aragão, Edward P. Mitchell, Carlos F. Frazão, Maria Arménia Carrondo and Peter F. Lindley  "Structural and functional relationships in the hybrid cluster protein family: structure of the  anaerobically purified hybrid cluster protein from Desulfovibrio vulgaris at 1.35 Å resolution"  Acta Crystallographica Section D, Biological Crystallography (2008) D64:665-674.

 June issue´s cover