title: Mechanistic diversity in a metalloenzyme superfamily.
abstract: It is now appreciated that the relationships of proteins, particularly enzymes, within a protein superfamily can be understood not only in terms of their sequence similarities and three-dimensional structures but also by chemical threads that relate their functional attributes. The mechanistic ties among superfamily members can often be traced to a common transition state for the rate-limiting step of the reactions being catalyzed. This paper presents an analysis of a metalloenzyme superfamily, the members of which catalyze a very diverse set of reactions with unrelated transition states but a more general common mechanistic imperative. The vicinal oxygen chelate (VOC) superfamily is composed of structurally related proteins with paired beta alpha beta beta beta motifs that provide a metal coordination environment with two or three open or readily accessible coordination sites to promote direct electrophilic participation of the metal ion in catalysis. The known types of reactions that are catalyzed include isomerizations (glyoxalase I), epimerizations (methylmalonyl-CoA epimerase), oxidative cleavage of C-C bonds (extradiol dioxygenase), and nucleophilic substitutions (fosfomycin resistance proteins). The remarkable access to mechanism space that is provided by the VOC superfamily appears to derive from a simple, pseudosymmetric structural fold that maximizes the catalytic versatility of the metal center.
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA. r.armstrong@vanderbilt.edu
authors.forename: R N
authors.initials: RN
authors.lastname: Armstrong
mesh_terms: D000079:Acetaldehyde / Q000737:chemistry; D000123:Acetyltransferases / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry; D001761:Bleomycin / Q000737:chemistry; D002614:Chelating Agents / Q000737:chemistry; D049308:Dioxygenases; D004352:Drug Resistance, Microbial; D005578:Fosfomycin / Q000737:chemistry; D005982:Glutathione Transferase / Q000737:chemistry*; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000737:chemistry*; D008667:Metalloproteins / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D010105:Oxygenases / Q000737:chemistry*; D019998:Racemases and Epimerases / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D002614:Chelating Agents; D008667:Metalloproteins; D001761:Bleomycin; D005578:Fosfomycin; D010105:Oxygenases; C023133:dihydroxynaphthalene oxygenase; D049308:Dioxygenases; C087954:bleomycin N-acetyltransferase; D000123:Acetyltransferases; D005982:Glutathione Transferase; D007791:Lactoylglutathione Lyase; D019998:Racemases and Epimerases; C021581:methylmalonyl-coenzyme A racemase; D000079:Acetaldehyde; D010100:Oxygen