FAD capping
Viral RNA-dependent RNA polymerase initiates transcription/replication at a flavin adenine dinucleotide (FAD), resulting in a 5'- FAD cap on viral RNAs. In this way, recognition of viral 5' RNA by host antiviral receptors can be bypassed.
Enzymatic reaction:
FAD nucleotidyltransferase (RNA-dependent)
RNA nucleotidyltransferase (RNA-dependent) EC 2.7.7.48 RHEA:21248
Mechanism
Viral RdRp are characterized by a conserved motif in which two conserved aspartic acid residues are bound to two magnesium ions. The reaction begins with the deprotonation of primer's 3' OH, in a manner that doesn't require a base . Subsequently, the 3'-oxygen acts as a nucleophile to attack the phosphate bond and eventually releases a pyrophosphate.
Hepatitis C virus RNA is 5'-capped with flavin adenine dinucleotide
Anna V Sherwood, Lizandro R Rivera-Rangel, Line A Ryberg, Helena S Larsen, Klara M Anker, Rui Costa, Cathrine B Vagbo, Eva Jakljevic, Long V Pham, Carlota Fernandez-Antunez, Gabriele Indrisiunaite, Agnieszka Podolska-Charlery, Julius E R Grothen, Nicklas W Langvad, Nicolas Fossat, Anna Offersgaard, Amal Al-Chaer, Louise Nielsen, Anna Kusnierczyk, Christina Solund, Nina Weis, Judith M Gottwein, Kenn Holmbeck, Sandro Bottaro, Santseharay Ramirez, Jens Bukh, Troels K H Scheel, Jeppe Vinther
Nature. 2023 Jul;619(7971):811-818.
A Structural Overview of RNA-Dependent RNA Polymerases from the Flaviviridae Family
Jiqin Wu, Weichi Liu, and Peng Gong
Int J Mol Sci. 2015 Jun; 16(6): 12943?12957
Multiple deprotonation paths of the nucleophile 3'-OH in the DNA synthesis reaction
Mark T Gregory, Yang Gao, Qiang Cui, Wei Yang
Proc Natl Acad Sci U S A. 2021 Jun 8;118(23):e2103990118.
