An aminotransferase branch point connects purine catabolism to amino acid recycling.
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.
Ramazzina
Ileana
I
Department of Biochemistry and Molecular Biology, University of Parma, Parma, Italy.
Costa
Roberto
R
Cendron
Laura
L
Berni
Rodolfo
R
Peracchi
Alessio
A
Zanotti
Giuseppe
G
Percudani
Riccardo
R
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
D000596:Amino Acids; D006038:Glyoxylates; D011687:Purines; C549215:ureidoglycine; D014508:Urea; D000637:Transaminases; D000409:Alanine; D005998:Glycine; C030985:purine