Phosphate group binding "cup" of PLP-dependent and non-PLP-dependent enzymes: leitmotif and variations.
Pyridoxal-5'-phosphate (PLP) is widely used by many enzymes in reactions where amino acids are interconverted. Whereas the role of the pyridoxal ring in catalysis is well understood, the functional role of the single phosphate group in PLP has been less studied. Here we construct unambiguous connection diagrams that describe the interactions among the three non-ester phosphate oxygen atoms of PLP and surrounding atoms from the protein binding site and from water molecules, the so-called phosphate group binding "cup". These diagrams provide a simple means to identify common recognition motifs for the phosphate group in both similar and different protein folds. Diagrams were constructed and compared in the cases of five newly determined structures of PLP-dependent transferases (fold type I enzymes) and, additionally, two non-PLP protein complexes (indole-3-glycerol phosphate synthase (IGPS) with bound indole-3-glycerol phosphate (IGP) and old yellow enzyme (OYE) with bound flavin mononucleotide (FMN)). A detailed comparison of the diagrams shows that three positions out of ten in the structure of the phosphate group binding "cup" contain invariant atoms, while seven others are occupied by conserved atom types. This level of similarity was also observed in the fold type III (TIM beta/alpha-barrel) enzymes that bind three different ligands: PLP, IGP and FMN.
Denesyuk
Alexander I
AI
Department of Biochemistry and Pharmacy, Abo Akademi University, Tykistökatu 6A, FIN-20521 Turku, Finland.
Denessiouk
Konstantin A
KA
Korpela
Timo
T
Johnson
Mark S
MS
D001665:Binding Sites; D002384:Catalysis; D005486:Flavin Mononucleotide / Q000378:metabolism; D012696:Glycine Hydroxymethyltransferase / Q000737:chemistry; D007209:Indole-3-Glycerol-Phosphate Synthase / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D011732:Pyridoxal Phosphate / Q000378:metabolism*; D000637:Transaminases / Q000737:chemistry
D010710:Phosphates; D011732:Pyridoxal Phosphate; D005486:Flavin Mononucleotide; D012696:Glycine Hydroxymethyltransferase; D000637:Transaminases; C053430:histidinol-phosphate aminotransferase; D007209:Indole-3-Glycerol-Phosphate Synthase