title: PLP and PMP radicals: a new paradigm in coenzyme B6 chemistry.
abstract: Enzymes frequently rely on a broad repertoire of cofactors to perform chemically challenging transformations. The B6 coenzymes, composed of pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP), are used by many transaminases, racemases, decarboxylases, and enzymes catalyzing alpha,beta and beta,gamma-eliminations. Despite the variety of reactions catalyzed by B6-dependent enzymes, the mechanism of almost all such enzymes is based on their ability to stabilize high-energy anionic intermediates in their reaction pathways by the pyridinium moiety of PLP/PMP. However, there are two notable exceptions to this model, which are discussed in this article. The first enzyme, lysine 2,3-aminomutase, is a PLP-dependent enzyme that catalyzes the interconversion of L-lysine to L-beta-lysine using a one-electron-based mechanism utilizing a [4Fe-4S] cluster and S-adenosylmethionine. The second enzyme, CDP-6-deoxy-L-threo-D-glycero-4-hexulose-3-dehydrase, is a PMP-dependent enzyme involved in the formation of 3,6-dideoxysugars in bacteria. This enzyme also contains an iron-sulfur cluster and uses a one-electron based mechanism to catalyze removal of a C-3 hydroxy group from a 4-hexulose. In both cases, the participation of free radicals in the reaction pathway has been established, placing these two B6-dependent enzymes in an exclusive class by themselves.
authors.affiliation: Division of Medicinal Chemistry, College of Pharmacy, University of Texas, Austin, Texas 78712, USA.
authors.forename: G
authors.initials: G
authors.lastname: Agnihotri
authors.forename: H W
authors.initials: HW
authors.lastname: Liu
mesh_terms: D002384:Catalysis; D005609:Free Radicals / Q000737:chemistry; D006836:Hydro-Lyases / Q000737:chemistry; D019751:Intramolecular Transferases / Q000737:chemistry; D007501:Iron / Q000737:chemistry; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D011732:Pyridoxal Phosphate / Q000737:chemistry*; D011733:Pyridoxamine / Q000031:analogs & derivatives* / Q000737:chemistry; D025101:Vitamin B 6 / Q000737:chemistry*
chemical_list: D005609:Free Radicals; D011732:Pyridoxal Phosphate; D011733:Pyridoxamine; D025101:Vitamin B 6; D007501:Iron; C073141:CDP-4-keto-6-deoxy-D-glucose-3-dehydrase; D006836:Hydro-Lyases; D019751:Intramolecular Transferases; C021518:lysine 2,3-aminomutase; C010627:pyridoxamine phosphate