Conformational Modulation of a Mobile Loop Controls Catalysis in the (βα)₈-Barrel Enzyme of Histidine Biosynthesis HisF.

ABSTRACT: The overall significance of loop motions for enzymatic activity is generally accepted. However, it has largely remained unclear whether and how such motions can control different steps of catalysis. We have studied this problem on the example of the mobile active site β₁α₁-loop (loop1) of the (βα)₈-barrel enzyme HisF, which is the cyclase subunit of imidazole glycerol phosphate synthase. Loop1 variants containing single mutations of conserved amino acids showed drastically reduced rates for the turnover of the substrates N'-[(5'-phosphoribulosyl) formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (PrFAR) and ammonia to the products imidazole glycerol phosphate (ImGP) and 5-aminoimidazole-4-carboxamide-ribotide (AICAR). A comprehensive mechanist

SUBMITTER: Hupfeld E 

PROVIDER: S-EPMC11350729 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature