Major and minor groove contacts in retroviral integrase-LTR interactions

Tan Wang, Mini Balakrishnan, Colleen Jonsson

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The 3'-processing activities of HIV-1, HTLV-2, and M-MuLV integrases (INs) with their corresponding U5 end of the vital DNA molecule were examined to define functional group determinants of U5 terminus recognition and catalysis. Nucleotide analogues were incorporated into the U5 terminus to produce conservative modifications in the surface of the major and/or minor grooves to map the hydrogen-bonding contacts required for LTR-IN interaction. Specifically, the phylogenetically conserved CA (positions 4 and 3, respectively) and the 5'-proximal nucleotide (position 5) were replaced with base analogues in plus and/or minus strands. For each integrase, similar major and minor groove contacts were identified in the guanine and adenine of the conserved CA/GT. Overall, perturbances in the minor groove resulted in a greater decrease in 3'-processing activity than the major groove substitutions. Additionally for HIV-1 and HTLV-2 INs, we observed an increase in the 3'-processing activity with an O4-MeThy substitution at position 3 of the minus strand. O4-MeThy may act to destabilize Watson-Crick base pairing and in doing so provide these INs with a more favorable interaction with the adjacent scissile bond. At position 5, a substantial divergence among the three INs was noted in the functional groups required for 3'-processing activity, thereby supporting the role of this position in providing some level of substrate specificity.

Original languageEnglish (US)
Pages (from-to)3624-3632
Number of pages9
JournalBiochemistry
Volume38
Issue number12
DOIs
StatePublished - Mar 23 1999
Externally publishedYes

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Integrases
Human T-lymphotropic virus 2
Processing
Functional groups
HIV-1
Substitution reactions
Nucleotides
Guanine
Adenine
Hydrogen Bonding
Substrate Specificity
Catalysis
Base Pairing
Hydrogen bonds
Molecules
DNA
Substrates

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Major and minor groove contacts in retroviral integrase-LTR interactions. / Wang, Tan; Balakrishnan, Mini; Jonsson, Colleen.

In: Biochemistry, Vol. 38, No. 12, 23.03.1999, p. 3624-3632.

Research output: Contribution to journalArticle

Wang, Tan ; Balakrishnan, Mini ; Jonsson, Colleen. / Major and minor groove contacts in retroviral integrase-LTR interactions. In: Biochemistry. 1999 ; Vol. 38, No. 12. pp. 3624-3632.
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