Structures of Pyridoxal 5′-Phosphate Synthase Reveal Mechanistic Details of the Single-enzyme Biosynthesis of a Critical Cofactor♦
Crystal Structures Capture Three States in the Catalytic Cycle of a Pyridoxal Phosphate (PLP) Synthase
♦ See referenced article, J. Biol. Chem. 2015, 290, 5226–5239
PLP synthase is a bacterial enzyme that makes pyridoxal 5′-phosphate (PLP) from glutamine, ribose 5-phosphate (R5P), and glyceraldehyde 3-phosphate (G3P). The enzyme has 12 subunits each of synthase and glutaminase; PLP, which is a cofactor for various reactions and is an active form of vitamin B6, is generated by the enzyme through three covalent intermediates. To better understand the complicated synthesis of PLP by this single enzyme, a team led by Janet Smith at the University of Michigan, Ann Arbor, described the characterization of crystals of the synthase active site in a Paper of the Week. The crystals captured the three steps of catalysis. The investigators found that the synthase goes back and forth between open and closed conformations, depending on the presence of the three substrates and the glutaminase. In the presence of glutamine and R5P, the enzyme's C-terminal tail becomes partially ordered to form a cover over the R5P site in the synthase's closed conformation. The synthase's closed conformation seems to be essential for the formation of one of the intermediates. The authors note, “Lack of PLP synthesis in humans suggests that the single-enzyme pathway may be a potential drug target.”
Conformational changes in the synthase active site. The image shows closure around an intermediate with glutamine in the active site.
- © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
