Effects of varying the spacing within the D,D-35-E motif in the catalytic region of retroviral integrase

Wesley M. Konsavage, Malgorzata Sudol, Michael Katzman

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The catalytic domain of all retroviral integrases contains an Asp,Asp-35-Glu (D,D-35-E) motif with precisely 35 amino acids between the second aspartate and the glutamate. We have now made several mutations designed to alter the length or flexibility of a mobile loop within this 35-amino-acid spacer region in full-length Rous sarcoma virus integrase. Surprisingly, most of the mutants had enzymatic activity, including ones that shortened or lengthened the loop by up to 6 amino acids. Several size mutants exhibited the two biologically relevant activities of integrase in reactions with Mn2+, although they were inactive with Mg2+. No viruses containing integrase with an altered length, however, replicated in cell culture, and these viruses were blocked at the integration step. Thus, the conserved 35-amino-acid spacing is not absolutely required for enzymatic activity, but the correlation between infectivity and Mg2+-dependent activity supports magnesium as the metal cofactor used by integrase in vivo.

Original languageEnglish (US)
Pages (from-to)223-233
Number of pages11
JournalVirology
Volume379
Issue number2
DOIs
StatePublished - Sep 30 2008

All Science Journal Classification (ASJC) codes

  • Virology

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