Linked Life Data

17319156

Source:http://linkedlifedata.com/resource/pubmed/id/17319156

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2007-2-26
pubmed:abstractText
Infectious diseases caused by flaviviruses are important emerging public health concerns and new vaccines and therapeutics are urgently needed. The NS3 protein from flavivirus is a multifunctional protein with protease, helicase and nucleoside 5' triphosphatase activities (NTPase). Thus, NS3 plays a crucial role in viral replication and represents an interesting target for the development of specific antiviral inhibitors. We have solved the structure of an enzymatically active fragment of the dengue virus NTPase/ helicase C-terminal catalytic domain in several related crystal forms. The structure is composed of three domains, bears an asymmetric distribution of charges and comprises a tunnel large enough to accommodate single strand RNA. A concave face formed by domains 2 and 3 is proposed to bind a nucleic acid duplex substrate. Comparison of the various copies of dengue and yellow fever virus NS3 NTPase/helicase catalytic domains reveals mobile regions of the enzyme. Such dynamic behaviour is likely to be coupled with directional translocation along the single strand nucleic acid substrate during strand separation. We used structure-based site directed mutagenesis to identify regions of the enzyme that are crucial for its ATPase or nucleic acid duplex unwinding activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1528-2511
pubmed:author
pubmed:issnType
Print
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
87-97; discussion 97-101, 251-3
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Towards the design of flavivirus helicase/NTPase inhibitors: crystallographic and mutagenesis studies of the dengue virus NS3 helicase catalytic domain.
pubmed:affiliation
School of Biological Sciences, Nanyang Technological University, 60, Nanyang Drive Singapore 637551.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't