A cofactor-dependent phosphoglycerate mutase homolog from Bacillus stearothermophilus is actually a broad specificity phosphatase

The distribution of phosphoglycerate mutase (PGM) activity in bacteria is c omplex, with some organisms possessing, both a cofactor-dependent and a cof actor-independent PGM and others having only one of these enzymes. Although Bacillus species contain only a cofactor-independent PGM, genes homologous to those encoding cofactor-dependent PGMs have been detected in this group of bacteria, but in at least one case the encoded protein lacks significan t PGM activity. Here we apply sequence analysis, molecular modeling, and en zymatic assays to the cofactor-dependent PGM homologs from B. stearothermop hilus and B. subtilis, and show that these enzymes are phosphatases with br oad substrate specificity. Homologs from other grampositive bacteria are al so likely to possess phosphatase activity. These studies clearly show that the exploration of genomic sequences through three-dimensional modeling is capable of producing useful predictions regarding function. However, signif icant methodological improvements will be needed before such analysis can b e carried out automatically.