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PMID: 19036793 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Functional and structural characterization of the integrase from the prototype foamy virus.

Nucleic acids research ·Vol. 37 ·No. 1 ·2009-01-00 ·Pages 243-55

Valkov E, Gupta SS, Hare S, Helander A, Roversi P, McClure M, Cherepanov P

Abstract

Establishment of the stable provirus is an essential step in retroviral replication, orchestrated by integrase (IN), a virus-derived enzyme. Until now, available structural information was limited to the INs of human immunodeficiency virus type 1 (HIV-1), avian sarcoma virus (ASV) and their close orthologs from the Lentivirus and Alpharetrovirus genera. Here, we characterized the in vitro activity of the prototype foamy virus (PFV) IN from the Spumavirus genus and determined the three-dimensional structure of its catalytic core domain (CCD). Recombinant PFV IN displayed robust and almost exclusively concerted integration activity in vitro utilizing donor DNA substrates as short as 16 bp, underscoring its significance as a model for detailed structural studies. Comparison of the HIV-1, ASV and PFV CCD structures highlighted both conserved as well as unique structural features such as organization of the active site and the putative host factor binding face. Despite possessing very limited sequence identity to its HIV counterpart, PFV IN was sensitive to HIV IN strand transfer inhibitors, suggesting that this class of inhibitors target the most conserved features of retroviral IN-DNA complexes.

MeSH Terms
Amino Acid Sequence Animals Catalytic Domain Cell Line Crystallography Dogs Enzyme Inhibitors/pharmacology Humans Integrases/chemistry,genetics,metabolism Models, Molecular Molecular Sequence Data Recombinant Proteins/chemistry,metabolism Sequence Analysis, DNA Spumavirus/enzymology Viral Proteins/chemistry,genetics,metabolism
Chemicals
Enzyme Inhibitors Recombinant Proteins Viral Proteins Integrases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Valkov Eugene
Division of Medicine, St. Mary's Campus, Imperial College London, London, UK.
Gupta Saumya Shree
Hare Stephen
Helander Anna
Roversi Pietro
McClure Myra
Cherepanov Peter
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkn938
Published
2009-01-00
Epub
2008-00-26
Pages
243-55
Language
English
Region
England
NLM ID
0411011
PMCID
PMC2615609
Subset
IM
Grants
Medical Research Council · G0500367 · United Kingdom
Medical Research Council · G0400389 · United Kingdom
Medical Research Council · G0600009 · United Kingdom
Databases
PDB
3DLR
External Links
PubMed source DOI: 10.1093/nar/gkn938 PMC Full Text View journal details
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