TARGET: RNA-dependent RNA polymerase

DESCRIPTION:
RNA-dependent RNA polymerase (RdRP), (RDR), or RNA replicase, is an enzyme (EC 2.7.7.48) that catalyzes the replication of RNA from an RNA template. This is in contrast to a typical DNA-dependent RNA polymerase, which catalyzes the transcription of RNA from a DNA template. RNA-dependent RNA polymerase (RdRp) is an essential protein encoded in the genomes of all RNA-containing viruses with no DNA stage. It catalyses synthesis of the RNA strand complementary to a given RNA template. The RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo), or a primer-dependent mechanism that utilizes a viral protein genome-linked (VPg) primer. The de novo initiation consists in the addition of a nucleotide tri-phosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product. All the RNA-directed RNA polymerases, and many DNA-directed polymerases, employ a fold whose organization has been likened to the shape of a right hand with three subdomains termed fingers, palm, and thumb. Only the palm subdomain, composed of a four-stranded antiparallel beta-sheet with two alpha-helices, is well conserved among all of these enzymes. In RdRp, the palm subdomain comprises three well-conserved motifs (A, B, and C). Motif A (D-x(4,5)-D) and motif C (GDD) are spatially juxtaposed; the Asp residues of these motifs are implied in the binding of Mg2+ and/or Mn2+. The Asn residue of motif B is involved in selection of ribonucleoside triphosphates over dNTPs and, thus, determines whether RNA rather than DNA is synthesized. The domain organization and the 3D structure of the catalytic centre of a wide range of RdPps, even those with a low overall sequence homology, are conserved. The catalytic centre is formed by several motifs containing a number of conserved amino acid residues.

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DRUG STRUCTURE OTHER TARGET TYPE(S) DNAtraffic related PROTEIN(S)
Ribavirin RNA
anti-viral treatment
RNA synthesis inhibitor
RNA-dependent RNA polymerase