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Enzyme evolution pictured by X-ray crystallography

Researchers solve structures of three different chelatases

Oeiras, 05.01.11

Blood owes its red colour to the essential hemoglobin cofactor, heme. Present in many other important proteins, hemes require the insertion of a specific metal ion in a ring of carbons and nitrogen atoms (porphyrin), a reaction performed by chelatase enzymes. ITQB researchers joined efforts with researchers from the University of Kent and Queen Mary University of London to reveal the molecular mechanism of cobaltochelatases. The article, now published in the Proceedings of the National Academy of Science USA, gives a beautiful evolutionary picture of the chelatase family.

The simplest of cobaltochelatases is a small protein of two subunits present in archaea, a separate group of single-cell microorganisms. In most other organisms, the cobaltochelatases are about twice as big, a result of a gene duplication and fusion event. Resorting to X-ray crystallography, researchers solved the structure of chelatases from three different organisms - Archaeoglobus fulgidus (archaea), Salmonella enterica (Gram-positive bacteria), and Desulfovibrio vulgaris (Gram-negative bacteria). Because A. fulgidus and S. enterica chelatases were caught with the porphyrin substrate and D. vulgaris chelatase with the cobalt ion, these structures provided molecular detail on the rearrangements that take place during the process of porphyrin chelation and insertion of cobalt.

ITQB researchers from the Macromolecular Crystallography Unit and the Molecular Genetics of Microbial Resistance Lab concentrated on the cobaltochelatase (CbiKP) from D. vulgaris, the more complex of these enzymes. A. fulgidus chelatase receives the substrate between two subunits; in S. enterica, these subunits maintain their structural identity but are fused in a single protein, the enzyme is actually a dimer with two matching active sites; D. vulgaris chelatase is a like a duplication of this dimer with two additional heme groups. Researchers found that, besides the four catalytic domains, the tetramer is organized in such a way that a central cavity with the potential for ligand binding is formed. Authors suggest that the cobaltochelatase (CbiKP) of D. vulgaris may have evolved an additional function, such as the transport of metals across the periplasmic space. 


Original Article

doi: 10.1073/pnas.1014298108 PNAS December 20, 2010 

Evolution in a family of chelatases facilitated by the introduction of active site asymmetry and protein oligomerization

Célia V. Romão, Dimitrios Ladakis, Susana A. L. Lobo, Maria A. Carrondo, Amanda A. Brindley, Evelyne Deeryb, Pedro M. Matias, Richard W. Pickersgillc, Lígia M. Saraiva, and Martin J. Warrenb



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