1rdr: Difference between revisions

[[Image:1rdr.gif|left|200px]]<br /><applet load="1rdr" size="350" color="white" frame="true" align="right" spinBox="true"  

BACKGROUND: The central player in the replication of RNA viruses is the viral RNA-dependent RNA polymerase. The 53 kDa poliovirus polymerase, together with other viral and possibly host proteins, carries out viral RNA replication in the host cell cytoplasm. RNA-dependent RNA polymerases comprise a distinct category of polymerases that have limited sequence similarity to reverse transcriptases (RNA-dependent DNA polymerases) and perhaps also to DNA-dependent polymerases. Previously reported structures of RNA-dependent DNA polymerases, DNA-dependent DNA polymerases and a DNA-dependent RNA polymerase show that structural and evolutionary relationships exist between the different polymerase categories. RESULTS: We have determined the structure of the RNA-dependent RNA polymerase of poliovirus at 2.6 A resolution by X-ray crystallography. It has the same overall shape as other polymerases, commonly described by analogy to a right hand. The structures of the 'fingers' and 'thumb' subdomains of poliovirus polymerase differ from those of other polymerases, but the palm subdomain contains a core structure very similar to that of other polymerases. This conserved core structure is composed of four of the amino acid sequence motifs described for RNA-dependent polymerases. Structure-based alignments of these motifs has enabled us to modify and extend previous sequence and structural alignments so as to relate sequence conservation to function. Extensive regions of polymerase-polymerase interactions observed in the crystals suggest an unusual higher order structure that we believe is important for polymerase function. CONCLUSIONS: As a first example of a structure of an RNA-dependent RNA polymerase, the poliovirus polymerase structure provides for a better understanding of polymerase structure, function and evolution. In addition, it has yielded insights into an unusual higher order structure that may be critical for poliovirus polymerase function.

1RDR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_poliovirus_1 Human poliovirus 1] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RDR OCA].  

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