Stanford University HIV Drug Resistance Database - A curated public database designed to represent, store, and analyze the divergent forms of data underlying HIV drug resistance.

Structures of Integrase

  1. PDB summary
  2. Sample integrase structures and their PDB numbers
  3. Major integrase raltegravir-resistance positions
  4. Major integrase elvitegravir-resistance positions
  5. Integrase N-terminal domain
  6. Integrase C-terminal domain

To retrieve HIV Integrase (IN) structures from the PDB, we performed an advanced query for structures having similar sequences (search parameters: BLAST search, e-value cutoff = 10-20, query sequence), and exported the data into a spreadsheet using the menu options on the left side of the page.

N-terminal & catalytic core domains (tetramer) 1K6Y
C-terminal & catalytic core domains (dimer) 1EX4
Catalytic core domain complexed with early prototype inhibitor (5CITEP) & Mg++ 1QS4
Catalytic core domain & LEDGF/p75 2B4J

HIV-1 integrase catalyzes the integration of viral DNA into the host genome, which occurs in two steps: 3' processing and strand transfer. 3' processing involves cleaving a GT dinucleotide from the 3' ends of each DNA strand which leaves 2-mer overhangs on each side. Strand transfer involves cleavage of the host DNA and ligation of viral DNA. The above figure shows three dimensional structure of the HIV-1 integrase catalytic core domain (CCD) indicating positions associated with raltegravir resistance. Atomic coordinates were obtained from a crystal structure of an integrase CCD complexed with a prototype inhibitor 5CITEP (1QS4) (Goldgur 1999). The inhibitor is shown as yellow spheres. Active site residues D64, D116, and E152 are shown as white sticks. Residues known to directly reduce raltegravir susceptibility are shown as red sticks (E92, E138, G140, Q148, and N155). Position 143 -- a residue at which three mutations Y143R/C/H reduce raltegravir susceptibility -- is not shown because it is part of a loop that crystallized poorly. F121Y (not shown) is selected in vitro by raltegravir but it has not been reported in vivo.

The three dimensional structure of the HIV-1 integrase catalytic core domain (CCD) indicating positions associated with HIV-1 drug resistance. Residues known to directly reduce elvitegravir susceptibility are shown (E92, E138, G140, Q148, and N155 -- which are also raltegravir-resistance positions shown as red sticks, as well as T66 and S147, which confer exclusively elvitegravir resistance, are shown as orange sticks). F121Y, P145S and Q146P reduce elvitegravir susceptibility but have not been reported in vivo.

The three-dimensional structure of HIV-1 integrase N terminal domain (NTD) crystallized as a CCD-NTD tetramer (1K6Y) (Wang 2001). The four CCD subdomains are shown in surface mode in different shades of grey and blue. The NTD subdomains encompassing residues 1 to 49 are illustrated with the conserved HHCC zinc binding motif as yellow sticks. The N-terminal domain is postulated to have roles in 3' processing and strand transfer (Chiu and Davies 2004).

Representation of the three-dimensional Y-shaped structure of HIV-1 integrase C terminal domain (CTD) encompassing residues 212 to 270 crystallized as a CCD-CTD dimer (1EX4) (Chen, 2000). The C-terminal domain binds DNA nonspecifically and has some role in 3' processing and strand transfer (Chiu and Davies 2004).