Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain

El pdf es la versión pre-print.

Detalles Bibliográficos
Autores: Nadal, Marta, Mas, Philippe J., Blanco, Alexandre G., Arnan, Carme, Solà, Maria, Hart, Darren J., Coll, Miquel
Tipo de recurso: artículo
Fecha de publicación:2010
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/32178
Acceso en línea:http://hdl.handle.net/10261/32178
Access Level:acceso abierto
Palabra clave:Crystal structures
Human cytomegalovirus
DNA encapsidation
Endonuclease inhibitor
Combinatorial library
id ES_cc3489a8fc6ff3e8e4e612aa18bc4e2a
oai_identifier_str oai:digital.csic.es:10261/32178
network_acronym_str ES
network_name_str España
repository_id_str
spelling Structure and inhibition of herpesvirus DNA packaging terminase nuclease domainNadal, MartaMas, Philippe J.Blanco, Alexandre G.Arnan, CarmeSolà, MariaHart, Darren J.Coll, MiquelCrystal structuresHuman cytomegalovirusDNA encapsidationEndonuclease inhibitorCombinatorial libraryEl pdf es la versión pre-print.During viral replication, herpesviruses package their DNA into the procapsid by means of the terminase protein complex. In human cytomegalovirus (herpesvirus 5), the terminase is composed of subunits UL89 and UL56. UL89 cleaves the long DNA concatemers into unit-length genomes of appropriate length for encapsidation. We used ESPRIT, a high-throughput screening method, to identify a soluble purifiable fragment of UL89 from a library of 18,432 randomly truncated ul89 DNA constructs. The purified protein was crystallized and its three-dimensional structure was solved. This protein corresponds to the key nuclease domain of the terminase and shows an RNase H/integrase-like fold. We demonstrate that UL89-C has the capacity to process the DNA and that this function is dependent on Mn2+ ions, two of which are located at the active site pocket. We also show that the nuclease function can be inactivated by raltegravir, a recently approved anti-AIDS drug that targets the HIV integrase.This study was supported by Ministerio de Ciencia e Innovación Grant BFU2008-02372/BMC (M.C.), Generalitat de Catalunya Grant 2009 SGR 1309 (M.C.), and the European Commission (Spine2-Complexes LSHG-CT-2006-031220).Peer reviewedNational Academy of Sciences (U.S.)201120112010info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/32178reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1073/pnas.1007144107info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/321782026-05-22T06:33:51Z
dc.title.none.fl_str_mv Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain
title Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain
spellingShingle Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain
Nadal, Marta
Crystal structures
Human cytomegalovirus
DNA encapsidation
Endonuclease inhibitor
Combinatorial library
title_short Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain
title_full Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain
title_fullStr Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain
title_full_unstemmed Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain
title_sort Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain
dc.creator.none.fl_str_mv Nadal, Marta
Mas, Philippe J.
Blanco, Alexandre G.
Arnan, Carme
Solà, Maria
Hart, Darren J.
Coll, Miquel
author Nadal, Marta
author_facet Nadal, Marta
Mas, Philippe J.
Blanco, Alexandre G.
Arnan, Carme
Solà, Maria
Hart, Darren J.
Coll, Miquel
author_role author
author2 Mas, Philippe J.
Blanco, Alexandre G.
Arnan, Carme
Solà, Maria
Hart, Darren J.
Coll, Miquel
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Crystal structures
Human cytomegalovirus
DNA encapsidation
Endonuclease inhibitor
Combinatorial library
topic Crystal structures
Human cytomegalovirus
DNA encapsidation
Endonuclease inhibitor
Combinatorial library
description El pdf es la versión pre-print.
publishDate 2010
dc.date.none.fl_str_mv 2010
2011
2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/32178
url http://hdl.handle.net/10261/32178
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1073/pnas.1007144107
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv National Academy of Sciences (U.S.)
publisher.none.fl_str_mv National Academy of Sciences (U.S.)
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419677583671296
score 15.81155

Similares en LA Referencia