title: Functional control of the binuclear metal site in the metallo-beta-lactamase-like fold by subtle amino acid replacements.
abstract: At present there are three protein families that share a common structural domain, the alphabeta/betaalpha fold of class B beta-lactamases: zinc beta-lactamases, glyoxalases II, and A-type flavoproteins. A detailed inspection of their superimposed structures was undertaken and showed that although these proteins contain binuclear metal sites in spatially equivalent positions, there are some subtle differences within the first ligand sphere that determine a distinct composition of metals. Although zinc beta-lactamases contain either a mono or a di-zinc center, the catalytically active form of glyoxalase II contains a mixed iron-zinc binuclear center, whereas A-type flavoproteins contain a di-iron site. These variations on the type of metal site found within a common fold are correlated with the subtle variations in the nature of the ligating amino acid residues and are discussed in terms of the different reactions catalyzed by each of the protein families. Correlation of these observations with sequence data results in the definition of a sequence motif that comprises the possible binuclear metal site ligands in this broad family. The evolution of the proteins sharing this common fold and factors modulating reactivity are also discussed.
authors.affiliation: Instituto de Tecnologia Química e Biológica (ITQB), Universidade Nova de Lisboa, APT 127, 2780-156 Oeiras, Portugal. gomes@itqb.unl.pt
authors.forename: Cláudio M
authors.initials: CM
authors.lastname: Gomes
authors.forename: Carlos
authors.initials: C
authors.lastname: Frazão
authors.forename: António V
authors.initials: AV
authors.lastname: Xavier
authors.forename: Jean
authors.initials: J
authors.lastname: Legall
authors.forename: Miguel
authors.initials: M
authors.lastname: Teixeira
mesh_terms: D019943:Amino Acid Substitution; D000596:Amino Acids / Q000737:chemistry*; D001409:Bacillus cereus / Q000201:enzymology; D001441:Bacteroides fragilis / Q000201:enzymology; D001665:Binding Sites; D003901:Desulfovibrio / Q000201:enzymology; D005420:Flavoproteins / Q000737:chemistry; D006801:Humans; D007477:Ions / Q000737:chemistry; D007501:Iron / Q000737:chemistry; D008670:Metals / Q000737:chemistry*; D008958:Models, Molecular; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000201:enzymology; D020539:Sequence Analysis, Protein; D020615:Stenotrophomonas maltophilia / Q000201:enzymology; D013869:Thiolester Hydrolases / Q000737:chemistry; D015032:Zinc / Q000737:chemistry; D001618:beta-Lactamases / Q000737:chemistry*; D000099301:Hydroxyacylglutathione Hydrolase
chemical_list: D000596:Amino Acids; D005420:Flavoproteins; D007477:Ions; D007501:Iron; D008670:Metals; D013869:Thiolester Hydrolases; D015032:Zinc; D001618:beta-Lactamases; D000099301:Hydroxyacylglutathione Hydrolase