Biochemical and structural studies of 6-carboxy-5,6,7,8-tetrahydropterin synthase reveal the molecular basis of catalytic promiscuity within the tunnel-fold superfamily.

ABSTRACT: 6-Pyruvoyltetrahydropterin synthase (PTPS) homologs in both mammals and bacteria catalyze distinct reactions using the same 7,8-dihydroneopterin triphosphate substrate. The mammalian enzyme converts 7,8-dihydroneopterin triphosphate to 6-pyruvoyltetrahydropterin, whereas the bacterial enzyme catalyzes the formation of 6-carboxy-5,6,7,8-tetrahydropterin. To understand the basis for the differential activities we determined the crystal structure of a bacterial PTPS homolog in the presence and absence of various ligands. Comparison to mammalian structures revealed that although the active sites are nearly structurally identical, the bacterial enzyme houses a His/Asp dyad that is absent from the mammalian protein. Steady state and time-resolved kinetic analysis of the reaction catalyzed by the

SUBMITTER: Miles ZD 

PROVIDER: S-EPMC4156044 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature