PDBsum entry 3l2v

Recombination/DNA

PDB id: 3l2v

Contents

Protein chains

365 a.a. *

163 a.a. *

DNA/RNA

Ligands

NH4

RLT

GOL ×4

Metals

_MN ×3

_ZN

* Residue conservation analysis

PDB id:

3l2v

Name:

Recombination/DNA

Title:

Crystal structure of the prototype foamy virus (pfv) intasome in complex with manganese and mk0518 (raltegravir)

Structure:

Integrase. Chain: a, b. Synonym: in, p42in. Engineered: yes. 5'-d( Ap Tp Tp Gp Tp Cp Ap Tp Gp Gp Ap Ap Tp Tp Tp Tp Gp Tp A)-3'. Chain: c. Engineered: yes. Other_details: 19 nucleotide preprocessed pfv donor DNA.

Source:

Human spumaretrovirus. Sfvcpz(hu). Organism_taxid: 11963. Strain: hsrv2. Gene: pol. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic: yes

Resolution:

3.20Å R-factor: 0.206 R-free: 0.232

Authors:

S.Hare,S.S.Gupta,P.Cherepanov

Key ref:

S.Hare et al. (2010). Retroviral intasome assembly and inhibition of DNA strand transfer. Nature, 464, 232-236. PubMed id: 20118915

Date:

15-Dec-09 Release date: 09-Feb-10

Protein chain

P14350  (POL_FOAMV) -  Pro-Pol polyprotein from Human spumaretrovirus

Seq: 1143 a.a.

Struc: 365 a.a.*

Protein chain

P14350  (POL_FOAMV) -  Pro-Pol polyprotein from Human spumaretrovirus

Seq: 1143 a.a.

Struc: 163 a.a.*

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

DNA/RNA chains

A-T-T-G-T-C-A-T-G-G-A-A-T-T-T-T-G-T-A 19 bases

T-A-C-A-A-A-A-T-T-C-C-A-T-G-A-C-A 17 bases

Enzyme reactions

• Enzyme class 2: Chains A, B: E.C.2.7.7.- - ?????
• Enzyme class 3: Chains A, B: E.C.2.7.7.49 - RNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 4: Chains A, B: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 5: Chains A, B: E.C.3.1.-.-
• Enzyme class 6: Chains A, B: E.C.3.1.26.4 - ribonuclease H.
• Reaction: Endonucleolytic cleavage to 5'-phosphomonoester.
• Enzyme class 7: Chains A, B: E.C.3.4.23.- - ?????

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

reference

Nature 464:232-236 (2010)

PubMed id: 20118915

Retroviral intasome assembly and inhibition of DNA strand transfer.

S.Hare, S.S.Gupta, E.Valkov, A.Engelman, P.Cherepanov.

ABSTRACT

Integrase is an essential retroviral enzyme that binds both termini of linear viral DNA and inserts them into a host cell chromosome. The structure of full-length retroviral integrase, either separately or in complex with DNA, has been lacking. Furthermore, although clinically useful inhibitors of HIV integrase have been developed, their mechanism of action remains speculative. Here we present a crystal structure of full-length integrase from the prototype foamy virus in complex with its cognate DNA. The structure shows the organization of the retroviral intasome comprising an integrase tetramer tightly associated with a pair of viral DNA ends. All three canonical integrase structural domains are involved in extensive protein-DNA and protein-protein interactions. The binding of strand-transfer inhibitors displaces the reactive viral DNA end from the active site, disarming the viral nucleoprotein complex. Our findings define the structural basis of retroviral DNA integration, and will allow modelling of the HIV-1 intasome to aid in the development of antiretroviral drugs.