title: Structural biology of the purine biosynthetic pathway.
abstract: Purine biosynthesis requires ten enzymatic transformations to generate inosine monophosphate. PurF, PurD, PurL, PurM, PurC, and PurB are common to all pathways, while PurN or PurT, PurK/PurE-I or PurE-II, PurH or PurP, and PurJ or PurO catalyze the same steps in different organisms. X-ray crystal structures are available for all 15 purine biosynthetic enzymes, including 7 ATP-dependent enzymes, 2 amidotransferases and 2 tetrahydrofolate-dependent enzymes. Here we summarize the structures of the purine biosynthetic enzymes, discuss similarities and differences, and present arguments for pathway evolution. Four of the ATP-dependent enzymes belong to the ATP-grasp superfamily and 2 to the PurM superfamily. The amidotransferases are unrelated, with one utilizing an N-terminal nucleophileglutaminase and the other utilizing a triad glutaminase. Likewise the tetrahydrofolate-dependent enzymes are unrelated. Ancestral proteins may have included a broad specificity enzyme instead of PurD, PurT, PurK, PurC, and PurP, and a separate enzyme instead of PurM and PurL.
authors: Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, NY 14853, USA.
authors: Y
authors: Y
authors: Zhang
authors: M
authors: M
authors: Morar
authors: S E
authors: SE
authors: Ealick
mesh_terms: D001665:Binding Sites / Q000235:genetics; D004798:Enzymes / Q000737:chemistry* / Q000235:genetics; D019143:Evolution, Molecular; D040461:Gene Components; D007291:Inosine Monophosphate / Q000096:biosynthesis; D008958:Models, Molecular; D015394:Molecular Structure; D011687:Purines / Q000096:biosynthesis*; D012265:Ribonucleotides / Q000096:biosynthesis
chemical_list: D004798:Enzymes; D011687:Purines; D012265:Ribonucleotides; D007291:Inosine Monophosphate