Linked Life Data

10762083

Source:http://linkedlifedata.com/resource/pubmed/id/10762083

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-6-9
pubmed:abstractText
2',5'-Oligoadenylate synthetase (2',5'-OAS) is a double-stranded RNA-dependent nucleotidyl-transferase induced by interferon (IFN). Several 2',5'-OAS cDNA have been cloned from human, pig, rat, mouse, and chicken. A P-loop motif followed by an Asp-containing sequence (referred to as D-box) and a region with a high content of Lys and Arg (KR-rich region) are well conserved in 2',5'-OAS. The sequence 196DFLKQR201 of 40-kDa human 2',5'-OAS, to which 8-azido-ATP binds (N. Kon and R.J. Suhadolnik, J. Biol. Chem. 271, 19983-19990, 1996), is included in the KR-rich region. We introduced several site-directed mutations into these active motifs of 42-kDa murine 2',5'-OAS. Each mutant enzyme studied bound to poly(I):poly(C) to the same extent as wild-type enzyme. Both K67R, a P-loop mutant, and K200R, a KR-rich region mutant, exhibited a reduced but considerable rate of enzymatic activities. The activity of the double mutant K67R/K200R was about 10% of the wild type. On the other hand, the activities of both K67M and K200M were not more than 2% of the wild-type enzyme, and no activity was detected in another P-loop mutant, G62A/G63A. The binding of Mg2+ to a D-box mutant D76N/D78N was markedly reduced, and only a very low level of enzymatic activity was detected in this mutant. These results demonstrate that the P-loop, the D-box that binds Mg2+, and the KR-rich region are important for the enzymatic activities of 2',5'-OAS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1079-9907
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
337-44
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Effects of specific mutations in active site motifs of 2',5'-oligoadenylate synthetase on enzymatic activity.
pubmed:affiliation
Department of Biotechnology, Kyoto Institute of Technology, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't