9F08

Nucleoside-2'-deoxyribosyltransferase from Lactobacillus leichmannii. Covalent complex with 2-deoxyribose.

Summary for 9F08

• Entry DOI: 10.2210/pdb9f08/pdb
• Descriptor: Nucleoside deoxyribosyltransferase, 2-deoxy-beta-D-erythro-pentofuranose (3 entities in total)
• Functional Keywords: nucleoside-2'-deoxyribosyltransferase, transferase
• Biological source: Lactobacillus leichmannii
• Total number of polymer chains: 2
• Total formula weight: 36464.97

Authors

Ascham, A.,Salihovic, A.,Burley, G.,Grogan, G. (deposition date: 2024-04-15, release date: 2024-12-04)

Primary citation

Salihovic, A.,Ascham, A.,Taladriz-Sender, A.,Bryson, S.,Withers, J.M.,McKean, I.J.W.,Hoskisson, P.A.,Grogan, G.,Burley, G.A.
Gram-scale enzymatic synthesis of 2'-deoxyribonucleoside analogues using nucleoside transglycosylase-2.
Chem Sci, 15:15399-15407, 2024

PubMed Abstract: Nucleosides are pervasive building blocks that are found throughout nature and used extensively in medicinal chemistry and biotechnology. However, the preparation of base-modified analogues using conventional synthetic methodology poses challenges in scale-up and purification. In this work, an integrated approach involving structural analysis, screening and reaction optimization, is established to prepare 2'-deoxyribonucleoside analogues catalysed by the type II nucleoside 2'-deoxyribosyltransferase from (NDT-2). Structural analysis in combination with substrate profiling, identified the constraints on pyrimidine and purine acceptor bases by NDT2. A solvent screen identifies pure water as a suitable solvent for the preparation of high value purine and pyrimidine 2'-deoxyribonucleoside analogues on a gram scale under optimized reaction conditions. This approach provides the basis to establish a convergent, step-efficient chemoenzymatic platform for the preparation of high value 2'-deoxyribonucleosides.

PubMed: 39234214
DOI: 10.1039/d4sc04938a

Experimental method

X-RAY DIFFRACTION (2.371 Å)