Functional attributes of the phosphate group binding cup of pyridoxal phosphate-dependent enzymes.
Twenty-four structures of pyridoxal-5'-phosphate (PLP)-dependent enzymes that represent five different folds are shown to share a common recognition pattern for the phosphate group of their PLP-ligands. All atoms that interact with the phosphate group of PLP in these proteins are organized within a two-layer structure so that the first interacting layer contains from five to seven atoms and parallel with this is a second layer containing from three to seven interacting atoms. In order to identify features of the phosphate-binding site common to PLP-dependent enzymes, a simple procedure is described that assigns relative positions to all interacting atoms unambiguously, such that the networks of interactions for different proteins can be compared. On the basis of these diagrams for 24 enzyme-cofactor complexes, a detailed comparison of the two-layer structures of PLP-dependent enzymes, with both similar and different folds, was made. A majority of the structurally defined PLP-dependent proteins use the same atom types in analogous "key" positions to bind their PLP-ligands. In some instances, proteins use water molecules when a key position is unoccupied. A similar two-layer recognition pattern extends to protein recognition of at least one other, non-PLP ligand, glucosamine 6-phosphate. We refer to this three-dimensional recognition pattern as the phosphate-binding cup. In general, the phosphate-binding cup provides a very stable anchoring point for PLP. When numerous water molecules occur within the cup, however, then the phosphate group of PLP participates directly in the enzymatic reactions with inorganic phosphate replacing the water molecules of the cup. With glucosamine-6-phosphate synthase, the water molecules of the phosphate-binding cup facilitate the entry of substrate and the exit of product.
Denesyuk
Alexander I
AI
Finnish-Russian Joint Biotechnology Laboratory, University of Turku, BioCity 6A, Turku, FIN-20520, Finland.
Denessiouk
Konstantin A
KA
Korpela
Timo
T
Johnson
Mark S
MS
D001665:Binding Sites; D002384:Catalysis; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D010710:Phosphates / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D021122:Protein Subunits; D011732:Pyridoxal Phosphate / Q000378:metabolism*
D004798:Enzymes; D008024:Ligands; D010710:Phosphates; D021122:Protein Subunits; D011732:Pyridoxal Phosphate