Topology of a DNA G-quadruplex structure formed in the HIV-1 promoter: a potential target for anti-HIV drug development. J Am Chem Soc 2014 Apr 09;136(14):5249-52
Date
03/22/2014Pubmed ID
24649937DOI
10.1021/ja501500cScopus ID
2-s2.0-84897980191 (requires institutional sign-in at Scopus site) 132 CitationsAbstract
Nucleic acid sequences containing guanine tracts are able to adopt noncanonical four-stranded nucleic acid structures called G-quadruplexes (G4s). These structures are based on the stacking of two or more G-tetrads; each tetrad is a planar association of four guanines held together by eight hydrogen bonds. In this study, we analyzed a conserved G-rich region from HIV-1 promoter that is known to regulate the transcription of the HIV-1 provirus. Strikingly, our analysis of an alignment of 1684 HIV-1 sequences from this region showed a high conservation of the ability to form G4 structures despite a lower conservation of the nucleotide primary sequence. Using NMR spectroscopy, we determined the G4 topology adopted by a DNA sequence from this region (HIV-PRO1: 5' TGGCCTGGGCGGGACTGGG 3'). This DNA fragment formed a stable two G-tetrad antiparallel G4 with an additional Watson-Crick CG base pair. This hybrid structure may be critical for HIV-1 gene expression and is potentially a novel target for anti-HIV-1 drug development.
Author List
Amrane S, Kerkour A, Bedrat A, Vialet B, Andreola ML, Mergny JLAuthor
Amina Bedrat PhD Postdoctoral Researcher 3 in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AcridinesAnti-HIV Agents
DNA, Viral
G-Quadruplexes
HIV-1
Ligands
Promoter Regions, Genetic
Structure-Activity Relationship