{PDOC50507}
{PS50507; RDRP_SSRNA_POS}
{PS50522; RDRP_PHAGE}
{PS50523; RDRP_DSRNA_REO}
{PS50524; RDRP_DSRNA_BIR}
{PS50525; RDRP_SSRNA_NEG_SEG}
{PS50526; RDRP_SSRNA_NEG_NONSEG}
{BEGIN}
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* RNA-directed RNA polymerase catalytic domain profiles *
*********************************************************

RNA-directed  RNA  polymerase  (RdRp)  (EC  2.7.7.48)  is an essential protein
encoded  in the genomes of all RNA containing viruses with no DNA stage [1,2].
It  catalyses  synthesis  of  the  RNA  strand  complementary  to  a given RNA
template,  but the precise molecular mechanism remains unclear. The postulated
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) mechanism. 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 [3].

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 (see <PDB:1RDR>) [4].
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 is synthesized rather than DNA [5].

RNA  viruses with no DNA stage can be placed in three main categories based on
their replication and coding strategies: positive single-stranded RNA (ssRNA),
negative   ssRNA   and  double-stranded  RNA  (dsRNA)  viruses.  To  recognize
RNA-directed RNA polymerase we have developed six profiles that roughly follow
this  classification  (see below). They are all directed against the catalytic
region (palm subdomain).

-Sequences known to belong to this class detected by the first profile:    ALL
 positive   ssRNA   viruses,   two   small  families  of  dsRNA  viruses:  the
 Partitiviridae  and  the  Totoviridae  and  some  eukaryotic RdRps.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the second profile:   ALL
 bacteriophages RdRps.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the third profile:    ALL
 RdRps of the Reoviridae family of dsRNA viruses.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the fourth profile:   ALL
 RdRps of the Birnaviridae family of dsRNA viruses.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the fifth profile:    ALL
 RdRps  of negative ssRNA viruses with segmented genomes except the ophiovirus
 and the varicovirus.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the sixth profile:    ALL
 RdRps   of  negative  ssRNA  viruses  with  non-segmented  genomes  plus  the
 ophiovirus and the varicovirus.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Note: The GDD motif lacks in Birnaviridae RNA-directed RNA polymerases [6].

-Last update: November 2005 / First entry.

[ 1] Koonin E.V., Gorbalenya A.E., Chumakov K.M.
     "Tentative identification of RNA-dependent RNA polymerases of dsRNA
     viruses and their relationship to positive strand RNA viral
     polymerases."
     FEBS Lett. 252:42-46(1989).
     PubMed=2759231
[ 2] Zanotto P.M., Gibbs M.J., Gould E.A., Holmes E.C.
     "A reevaluation of the higher taxonomy of viruses based on RNA
     polymerases."
     J. Virol. 70:6083-6096(1996).
     PubMed=8709232
[ 3] Kao C.C., Singh P., Ecker D.J.
     "De novo initiation of viral RNA-dependent RNA synthesis."
     Virology 287:251-260(2001).
     PubMed=11531403; DOI=10.1006/viro.2001.1039
[ 4] Hansen J.L., Long A.M., Schultz S.C.
     "Structure of the RNA-dependent RNA polymerase of poliovirus."
     Structure 5:1109-1122(1997).
     PubMed=9309225
[ 5] Gohara D.W., Crotty S., Arnold J.J., Yoder J.D., Andino R.,
     Cameron C.E.
     "Poliovirus RNA-dependent RNA polymerase (3Dpol): structural,
     biochemical, and biological analysis of conserved structural motifs A
     and B."
     J. Biol. Chem. 275:25523-25532(2000).
     PubMed=10827187; DOI=10.1074/jbc.M002671200
[ 6] Shwed P.S., Dobos P., Cameron L.A., Vakharia V.N., Duncan R.
     "Birnavirus VP1 proteins form a distinct subgroup of RNA-dependent RNA
     polymerases lacking a GDD motif."
     Virology 296:241-250(2002).
     PubMed=12069523; DOI=10.1006/viro.2001.1334

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