Evidence Supporting Substrate Channeling between Domains of Human PAICS: A Time-Course Analysis of ¹³C-Bicarbonate Incorporation.

ABSTRACT: Human phosphoribosylaminoimidazole carboxylase phosphoribosylaminoimdiazole succinocarboxamide synthetase (PAICS) is a dual activity enzyme catalyzing two consecutive reactions in de novo purine nucleotide synthesis. Crystallographic structures of recombinant human PAICS suggested the channeling of 4-carboxy-5-aminoimidazole-1-ribose-5'-phosphate (CAIR) between two active sites of PAICS, while a prior work of an avian PAICS suggested otherwise. Here, we present time-course mass spectrometric data supporting the channeling of CAIR between domains of recombinant human PAICS. Time-course mass spectral analysis showed that CAIR added to the bulk solution (CAIR^bulk) is decarboxylated and re-carboxylated before the accumulation of succinyl-5-aminoimidazole-4-carboxamide-1-ribos

SUBMITTER: Shon H 

PROVIDER: S-EPMC8988938 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature