2r7j
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= S8, SEGMENT 8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= Simian rotavirus A/SA11]) | |GENE= S8, SEGMENT 8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= Simian rotavirus A/SA11]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1l9v|1l9v]], [[2r7c|2R7C]], [[2r7p|2R7P]], [[2r8f|2R8F]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2r7j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r7j OCA], [http://www.ebi.ac.uk/pdbsum/2r7j PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2r7j RCSB]</span> | ||
}} | }} | ||
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[[Category: rotavirus]] | [[Category: rotavirus]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:57:24 2008'' |
Revision as of 01:57, 31 March 2008
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| , resolution 2.6Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | S8, SEGMENT 8 (Simian rotavirus A/SA11) | ||||||
| Related: | 1l9v, 2R7C, 2R7P, 2R8F
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of rotavirus non structural protein NSP2 with H225A mutation
Overview
Rotavirus, the major pathogen of infantile gastroenteritis, carries a nonstructural protein, NSP2, essential for viroplasm formation and genome replication/packaging. In addition to RNA-binding and helix-destabilizing properties, NSP2 exhibits nucleoside triphosphatase activity. A conserved histidine (H225) functions as the catalytic residue for this enzymatic activity, and mutation of this residue abrogates genomic double-stranded RNA synthesis without affecting viroplasm formation. To understand the structural basis of the phosphatase activity of NSP2, we performed crystallographic analyses of native NSP2 and a functionally defective H225A mutant in the presence of nucleotides. These studies showed that nucleotides bind inside a cleft between the two domains of NSP2 in a region that exhibits structural similarity to ubiquitous cellular HIT (histidine triad) proteins. Only minor conformational alterations were observed in the cleft upon nucleotide binding and hydrolysis. This hydrolysis involved the formation of a stable phosphohistidine intermediate. These observations, reminiscent of cellular nucleoside diphosphate (NDP) kinases, prompted us to investigate whether NSP2 exhibits phosphoryl-transfer activity. Bioluminometric assay showed that NSP2 exhibits an NDP kinase-like activity that transfers the bound phosphate to NDPs. However, NSP2 is distinct from the highly conserved cellular NDP kinases in both its structure and catalytic mechanism, thus making NSP2 a potential target for antiviral drug design. With structural similarities to HIT proteins, which are not known to exhibit NDP kinase activity, NSP2 represents a unique example among structure-activity relationships. The newly observed phosphoryl-transfer activity of NSP2 may be utilized for homeostasis of nucleotide pools in viroplasms during genome replication.
About this Structure
2R7J is a Single protein structure of sequence from Simian rotavirus a/sa11. Full crystallographic information is available from OCA.
Reference
Crystallographic and biochemical analysis of rotavirus NSP2 with nucleotides reveals a nucleoside diphosphate kinase-like activity., Kumar M, Jayaram H, Vasquez-Del Carpio R, Jiang X, Taraporewala ZF, Jacobson RH, Patton JT, Prasad BV, J Virol. 2007 Nov;81(22):12272-84. Epub 2007 Sep 5. PMID:17804496
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