title: An aminotransferase branch point connects purine catabolism to amino acid recycling.
abstract: Although amino acids are known precursors of purines, a pathway for the direct recycling of amino acids from purines has never been described at the molecular level. We provide NMR and crystallographic evidence that the PucG protein from Bacillus subtilis catalyzes the transamination between an unstable intermediate ((S)-ureidoglycine) and the end product of purine catabolism (glyoxylate) to yield oxalurate and glycine. This activity enables soil and gut bacteria to use the animal purine waste as a source of carbon and nitrogen. The reaction catalyzed by (S)-ureidoglycine-glyoxylate aminotransferase (UGXT) illustrates a transamination sequence in which the same substrate provides both the amino group donor and, via its spontaneous decay, the amino group acceptor. Structural comparison and mutational analysis suggest a molecular rationale for the functional divergence between UGXT and peroxisomal alanine-glyoxylate aminotransferase, a fundamental enzyme for glyoxylate detoxification in humans.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Parma, Parma, Italy.
authors.forename: Ileana
authors.initials: I
authors.lastname: Ramazzina
authors.forename: Roberto
authors.initials: R
authors.lastname: Costa
authors.forename: Laura
authors.initials: L
authors.lastname: Cendron
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Berni
authors.forename: Alessio
authors.initials: A
authors.lastname: Peracchi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zanotti
authors.forename: Riccardo
authors.initials: R
authors.lastname: Percudani
mesh_terms: D000409:Alanine / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D001412:Bacillus subtilis / Q000201:enzymology*; D055162:Biocatalysis; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D006038:Glyoxylates / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009154:Mutation; D010802:Phylogeny; D011687:Purines / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D000637:Transaminases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism
chemical_list: D000596:Amino Acids; D006038:Glyoxylates; D011687:Purines; C549215:ureidoglycine; D014508:Urea; D000637:Transaminases; D000409:Alanine; D005998:Glycine; C030985:purine