PDBsum entry: 1exq

Viral protein

PDB id: 1exq

Contents

Protein chains

147 a.a. *

Ligands

SO4 ×4

Metals

_CD ×4

_CL ×2

Waters ×99

* Residue conservation analysis

PDB id:

1exq

Name:

Viral protein

Title:

Crystal structure of the HIV-1 integrase catalytic core domain

Structure:

Pol polyprotein. Chain: a, b. Fragment: HIV-1 integrase catalytic core. Engineered: yes. Mutation: yes

Source:

Human immunodeficiency virus 1. Organism_taxid: 11676. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

1.60Å R-factor: 0.253 R-free: 0.271

Authors:

J.C-H.Chen,J.Krucinski,L.J.W.Miercke,J.S.Finer-Moore, A.H.Tang,A.D.Leavitt,R.M.Stroud

Key ref:

J.C.Chen et al. (2000). Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: a model for viral DNA binding. Proc Natl Acad Sci U S A, 97, 8233-8238. PubMed id: 10890912 DOI: 10.1073/pnas.150220297

Date:

03-May-00 Release date: 03-Nov-00

Protein chains

P04585  (POL_HV1H2) -  Gag-Pol polyprotein

Seq: 1435 a.a.

Struc: 147 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.2.7.7.49 - RNA-directed Dna polymerase.
• Reaction: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
• Enzyme class 2: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
• Enzyme class 3: E.C.3.1.13.2 - Exoribonuclease H.
• Reaction: Exonucleolytic cleavage to 5'-phosphomonoester oligonucleotides in both 5'- to 3'- and 3'- to 5'-directions.
• Enzyme class 4: E.C.3.1.26.13 - Retroviral ribonuclease H.
• Enzyme class 5: E.C.3.4.23.16 - HIV-1 retropepsin.
• Reaction: Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Biological process: DNA integration (1 term)
• Biochemical function: nucleic acid binding (2 terms)

reference

DOI no: 10.1073/pnas.150220297

Proc Natl Acad Sci U S A 97:8233-8238 (2000)

PubMed id: 10890912

Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: a model for viral DNA binding.

J.C.Chen, J.Krucinski, L.J.Miercke, J.S.Finer-Moore, A.H.Tang, A.D.Leavitt, R.M.Stroud.

ABSTRACT

Insolubility of full-length HIV-1 integrase (IN) limited previous structure analyses to individual domains. By introducing five point mutations, we engineered a more soluble IN that allowed us to generate multidomain HIV-1 IN crystals. The first multidomain HIV-1 IN structure is reported. It incorporates the catalytic core and C-terminal domains (residues 52-288). The structure resolved to 2.8 A is a Y-shaped dimer. Within the dimer, the catalytic core domains form the only dimer interface, and the C-terminal domains are located 55 A apart. A 26-aa alpha-helix, alpha6, links the C-terminal domain to the catalytic core. A kink in one of the two alpha6 helices occurs near a known proteolytic site, suggesting that it may act as a flexible elbow to reorient the domains during the integration process. Two proteins that bind DNA in a sequence-independent manner are structurally homologous to the HIV-1 IN C-terminal domain, suggesting a similar protein-DNA interaction in which the IN C-terminal domain may serve to bind, bend, and orient viral DNA during integration. A strip of positively charged amino acids contributed by both monomers emerges from each active site of the dimer, suggesting a minimally dimeric platform for binding each viral DNA end. The crystal structure of the isolated catalytic core domain (residues 52-210), independently determined at 1.6-A resolution, is identical to the core domain within the two-domain 52-288 structure.

Selected figure(s)

Figure 1.
Fig. 1. HIV-1 IN activities. A schematic diagram of HIV-1 IN activities depicts the double-stranded DNA viral genome at the top as parallel black lines with the terminal nucleotides CAGT. The conserved 3' CA dinucleotide is underlined at each viral end. IN first acts in the cytoplasm to remove the two 3' nucleotides (3' processing), leaving a 2-nt overhang at each 5' end. In the nucleus, IN mediates a concerted integration (strand transfer) by ligating each 3' end of the viral DNA (looped structure) to the host DNA (striped lines). This generates a "gapped intermediate" with free viral 5' ends that are repaired to generate the fully integrated provirus. The characteristic HIV-1 5-bp staggered strand transfer is depicted by the letters A-E in the target DNA, and the resulting 5-bp direct repeats (DR) of host DNA flanking the provirus are indicated.

Figure 2.
Fig. 2. Structure of HIV-1 IN52-288. (a) Stereoview of the HIV-1 IN52-288 dimer, composed of monomer A (blue) and monomer B (green). Monomer B catalytic residues D64, D116, and E152 are indicated (brown dots), and the N and C termini of each monomer are labeled. Immunologically critical residue W235 is located on the surface. Mutated residues C56S, W131D, F139D, and F185K are indicated, except for C280S, which is disordered. (b) The HIV-1 IN52-288 dimer rotated by 90° with respect to a. Catalytic residues are highlighted in brown. (c) Alignment of residues 195-210 in 6 demonstrates the kink at T210 that creates a 90° rotation of the C-terminal domains relative to one another as illustrated by the position of P233. Figure was generated by MOLSCRIPT (44) and RASTER3D (45).

Figures were selected by an automated process.