Structural highlights
Function
[NTD_LACLE] Catalyzes the cleavage of the glycosidic bond of 2'-deoxyribonucleosides and the transfer of the deoxyribosyl moiety to an acceptor purine or pyrimidine base.[1] [2]
Publication Abstract from PubMed
A large number of nucleoside analogs and 2'- deoxynucleoside triphosphates (dNTPs) have been synthesized in order to interfere with DNA metabolism. However, in vivo the concentration and phosphorylation of these analogues are key limiting factors. In this context, we designed enzymes to switch nucleobases attached to a deoxyribose monophosphate. Active chimeras were made from two distantly related enzymes: a nucleoside deoxyribosyltransferase (NDT) from lactobacilli and a 5'-monophosphate-2'-deoxyribonucleoside hydrolase (Rcl) from rat. Then, their unprecedented activity was further extended to deoxyribose triphosphate and, in vitro biosyntheses could be successfully performed with several base analogues. These new enzymes provide new tools to synthesize dNTPs analogs and to deliver them into cells.
Phosphodeoxyribosyltransferases: designed enzymes for deoxyribonucleotide synthesis.,Kaminski PA, Labesse G J Biol Chem. 2013 Jan 16. PMID:23325804[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Porter DJ, Merrill BM, Short SA. Identification of the active site nucleophile in nucleoside 2-deoxyribosyltransferase as glutamic acid 98. J Biol Chem. 1995 Jun 30;270(26):15551-6. PMID:7797550
- ↑ Armstrong SR, Cook WJ, Short SA, Ealick SE. Crystal structures of nucleoside 2-deoxyribosyltransferase in native and ligand-bound forms reveal architecture of the active site. Structure. 1996 Jan 15;4(1):97-107. PMID:8805514
- ↑ Kaminski PA, Labesse G. Phosphodeoxyribosyltransferases: designed enzymes for deoxyribonucleotide synthesis. J Biol Chem. 2013 Jan 16. PMID:23325804 doi:http://dx.doi.org/10.1074/jbc.M112.446492
