2025/01/01 by Rachel M. Mitton-Fry, René Rasche, Ann‐Marie Lawrence‐Dörner +5 · 1 voice
Biochemistry, Genetics and Molecular Biology · Materials Science · Medicine · #Coagulation, Bradykinin, Polyphosphates, and Angioedema #Enzyme function and inhibition #biodegradable polymer synthesis and properties
paper · pdf · doi:10.1039/d5cb00108k
openalex publication_date 2025/01/01 · openalex created_date 2025/07/08 · openalex updated_date 2026/08/01
bacterium (EbPPK2). The enzyme is highly promiscuous, accepting a range of NMPs with purine modifications. EbPPK2 efficiently catalyses the formation of the corresponding di-, tri- and tetraphosphates, typically with >70% conversion to the NTP. Slower conversion was observed for analogues with oxo- or thio-substitutions at the C6-position. To better understand nucleotide binding and catalysis, we determined the crystal structure of EbPPK2 at 1.7 Å resolution bound to a non-hydrolysable ATP analogue and polyphosphate. This enabled structure-guided design of EbPPK2 variants that efficiently convert GMP analogues, while retaining activity for AMP. Apart from being the preferred industrial-scale ATP recycling catalyst, EbPPK2 and variants bear potential to become the favoured enzyme family for purine-modified NTP production.