Non-cryogenic structure and dynamics of HIV-1 integrase catalytic core domain by X-ray free-electron lasers

Jae Hyun Park, Ji Hye Yun, Yingchen Shi, Jeongmin Han, Xuanxuan Li, Zeyu Jin, Taehee Kim, Jaehyun Park, Sehan Park, Haiguang Liu, Weontae Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

HIV-1 integrase (HIV-1 IN) is an enzyme produced by the HIV-1 virus that integrates genetic material of the virus into the DNA of infected human cells. HIV-1 IN acts as a key component of the Retroviral Pre-Integration Complex (PIC). Protein dynamics could play an important role during the catalysis of HIV-1 IN; however, this process has not yet been fully elucidated. X-ray free electron laser (XFEL) together with nuclear magnetic resonance (NMR) could provide information regarding the dynamics during this catalysis reaction. Here, we report the non-cryogenic crystal structure of HIV-1 IN catalytic core domain at 2.5 Å using microcrystals in XFELs. Compared to the cryogenic structure at 2.1 Å using conventional synchrotron crystallography, there was a good agreement between the two structures, except for a catalytic triad formed by Asp64, Asp116, and Glu152 (DDE) and the lens epithelium-derived growth factor binding sites. The helix III region of the 140-153 residues near the active site and the DDE triad show a higher dynamic profile in the non-cryogenic structure, which is comparable to dynamics data obtained from NMR spectroscopy in solution state.

Original languageEnglish
Article number1943
JournalInternational journal of molecular sciences
Volume20
Issue number8
DOIs
Publication statusPublished - 2019 Apr 2

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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