Conserved core structure and active site residues in alkaline phosphatase superfamily enzymes.
Cofactor-independent phosphoglycerate mutase (iPGM) has been previously identified as a member of the alkaline phosphatase (AlkP) superfamily of enzymes, based on the conservation of the predicted metal-binding residues. Structural alignment of iPGM with AlkP and cerebroside sulfatase confirmed that all these enzymes have a common core structure and revealed similarly located conserved Ser (in iPGM and AlkP) or Cys (in sulfatases) residues in their active sites. In AlkP, this Ser residue is phosphorylated during catalysis, whereas in sulfatases the active site Cys residues are modified to formylglycine and sulfatated. Similarly located Thr residue forms a phosphoenzyme intermediate in one more enzyme of the AlkP superfamily, alkaline phosphodiesterase/nucleotide pyrophosphatase PC-1 (autotaxin). Using structure-based sequence alignment, we identified homologous Ser, Thr, or Cys residues in other enzymes of the AlkP superfamily, such as phosphopentomutase, phosphoglycerol transferase, phosphonoacetate hydrolase, and GPI-anchoring enzymes (glycosylphosphatidylinositol phosphoethanolamine transferases) MCD4, GPI7, and GPI13. We predict that catalytical cycles of all the enzymes of AlkP superfamily include phosphoenzyme (or sulfoenzyme) intermediates.
Galperin
M Y
MY
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA. galperin@ncbi.nlm.nih.gov
Jedrzejas
M J
MJ
D000469:Alkaline Phosphatase / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D020134:Catalytic Domain / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics*; D030562:Databases, Protein; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D010736:Phosphoglycerate Mutase / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D016415:Sequence Alignment; D013429:Sulfatases / Q000235:genetics*
D000469:Alkaline Phosphatase; D013429:Sulfatases; D010736:Phosphoglycerate Mutase