Integrase

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<StructureSection load='3fx5' size='340' side='right' caption='HIV protease complex with inhibitor and glycerol (PDB code 3fx5)' scene=> Best example is PDB entry 3fx5 and is shown in the viewer.
Molecule Integrase, also known as Integrase, p2B, p10, Capsid protein p27, p4, p3, Reverse transcriptase beta-subunit, Protease p15, Nucleocapsid protein p12, Reverse transcriptase alpha-subunit, RT-alpha, p2A, RT-beta, Gag-Pro-Pol polyprotein, pp32, Matrix protein p19, IN, Matrix protein p17, Transframe peptide, Reverse transcriptase/ribonuclease H, Pr160Gag-Pol, Spacer peptide 1, p2, Exoribonuclease H, p6*, Gag-Pol polyprotein, Nucleocapsid protein p7, p15, Retropepsin, p6-pol, p66 RT, Protease, PR, CA, TF, NC, SP1, Capsid protein p24, MA, p51 RT, Ribonuclease H, Protease/Reverse transcriptase, Pro-Pol polyprotein, Pr125Pol, Protease/Reverse transcriptase/ribonuclease H, RNase H, p87Pro-RT-RNaseH, p42In, p65Pro-RT, INT, Pol polyprotein, dUTPase, RT, Deoxyuridine 5'-triphosphate nucleotidohydrolase, P72, Pr170Gag-Pol, p11, p2L, Capsid protein p26, Matrix protein p16, P119, Putative prophage integrase, Int protein, CP4-like integrase, Transposase from transposon Tn916, NC-pro, Pr160Gag-Pro-Pol, Nucleocapsid protein p15-pro, p1 and NC'.

FunctionFunction

Integrase: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.Data source: Uniprot P03367

Catalytic ActivityCatalytic Activity

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).Data source: Uniprot P03367

DiseaseDisease

RelevanceRelevance

Structural highlightsStructural highlights

Biological processBiological process

Is involved in the following biological processes:
proteolysis
DNA integration
RNA-dependent DNA replication
viral process
dUTP metabolic process
DNA recombination
establishment of integrated proviral latency
viral entry into host cell

In structuresIn structures

Integrase is found in 1103 PDB entries

  • Viruses (1062 PDB entries):
    • Human immunodeficiency virus 1 (550 PDB entries):
      • 3fx5
      • Title: Structure of HIV-1 Protease in Complex with Potent Inhibitor KNI-272 Determined by High Resolution X-ray Crystallography
      • 0.93 A resolution
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    • HIV-1 M:B_HXB2R (71 PDB entries):
    • Human immunodeficiency virus type 1 BH10 (69 PDB entries):
    • Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE) (52 PDB entries):
      • 3avj
      • Title: Crystal structures of novel allosteric peptide inhibitors of HIV integrase in the LEDGF binding site
      • 1.7 A resolution
      • Other macromolecules also in this entry: LEDGF peptide..
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    • HIV-1 M:B_ARV2/SF2 (46 PDB entries):
      • 4obj
      • Title: Crystal Structure of Inactive HIV-1 Protease in Complex with the p1-p6 substrate variant (S451N)
      • 1.75 A resolution
      • Other macromolecules also in this entry: Spacer peptide 2..
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    • Human immunodeficiency virus type 1 (BRU ISOLATE) (45 PDB entries):
    • Human spumaretrovirus (44 PDB entries):
      • 3oym
      • Title: Crystal structure of the PFV N224H mutant intasome bound to manganese
      • 2.02 A resolution
      • Other macromolecules also in this entry: DNA (5'-D(*AP*TP*TP*GP*TP*CP*AP*TP*GP*GP*AP*AP*TP*TP*TP*CP*GP*CP*A)-3'), DNA (5'-D(*TP*GP*CP*GP*AP*AP*AP*TP*TP*CP*CP*AP*TP*GP*AP*CP*A)-3').
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    • Human immunodeficiency virus (41 PDB entries):
    • Human immunodeficiency virus type 1 (Z2/CDC-Z34 ISOLATE) (16 PDB entries):
      • 2wkz
      • Title: HIV-1 Protease Inhibitors Containing a Tertiary Alcohol in the Transition-State Mimic with Improved Cell-Based Antiviral Activity
      • 1.7 A resolution
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    • Feline immunodeficiency virus (13 PDB entries):
      • 1fiv
      • Title: STRUCTURE OF AN INHIBITOR COMPLEX OF PROTEINASE FROM FELINE IMMUNODEFICIENCY VIRUS
      • 2.0 A resolution
      • Other macromolecules also in this entry: FIV PROTEASE INHIBITOR ACE-ALN-VAL-STA-GLU-ALN-NH2..
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    • Human immunodeficiency virus type 1 (BH5 ISOLATE) (12 PDB entries):
    • Rous sarcoma virus (strain Schmidt-Ruppin) (11 PDB entries):
    • Human immunodeficiency virus type 2 (ISOLATE ROD) (8 PDB entries):
    • Avian sarcoma virus (7 PDB entries):
    • Human immunodeficiency virus type 1 (CLONE 12) (5 PDB entries):
    • HUMAN IMMUNODEFICIENCY VIRUS 1 (4 PDB entries):
      • 2j9k
      • Title: Atomic-resolution Crystal Structure of Chemically-Synthesized HIV-1 Protease Complexed with Inhibitor MVT-101
      • 1.2 A resolution
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    • Rous sarcoma virus - Prague C (3 PDB entries):
    • Bovine immunodeficiency virus R29 (2 PDB entries):
    • Streptomyces phage phiC31 (1 PDB entries):
      • 4bqq
      • Title: Protein crystal structure of the N-terminal and recombinase domains of the Streptomyces temperate phage serine recombinase, fC31 integrase.
      • 2.15 A resolution
  • Bacteria (10 PDB entries):
    • Enterococcus faecalis (4 PDB entries):
    • Yersinia pestis (2 PDB entries):
    • Staphylococcus aureus subsp. aureus USA300_TCH1516 (1 PDB entries):
      • 3nkh
      • Title: Crystal Structure of Integrase from MRSA strain Staphylococcus aureus
      • 2.502 A resolution
  • Eukaryota (3 PDB entries):
    • Homo sapiens (3 PDB entries):
      • 3ufn
      • Title: Crystal Structure of Multidrug Resistant HIV-1 Protease Clinical Isolate PR20 in Complex with Saquinavir
      • 1.45 A resolution
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3D structures of integrase3D structures of integrase

Updated on 04-September-2018 {{#tree:id=OrganizedByTopic|openlevels=0|

  • Integrase
    • 3bvp – Integrase N-terminal – Lactococcus phage
    • 2oxo – LamInt binding domain – phage
    • 1kjk – EpLamInt N-terminal – NMR
    • 1ae9 – EpLamInt catalytic core
    • 1aih – HP1 integrase catalytic domain – bacteriophage
    • 3nrw – INT/site-specific recombinase N-terminal – Haloarcula marismortui
    • 3jtz – INT arm-type binding domain – Yersinia pestis
    • 3ju0 – HPI INT arm-type binding domain – Pectobacterium atrosepticum
    • 2kkp – INT SAM-like domain – Moorella thermoacetica – NMR
    • 2kkv – INT fragment – Salmonella enterica – NMR
    • 2khq - INT fragment – Staphylococcus saprophyticus – NMR
    • 5cz1 – INT catalytic domain – mouse mammary tumor virus
    • 5dor, 5c6k – INT catalytic domain – Enterobacteria phage P2
    • 2khv, 2kj5 – INT residues 102-199 – Nitrosospira multiformis – NMR
    • 5t3a – VMvINT – Visna/Maedi virus
    • 5llj – VMvINT C terminal
    • 4pa1 – FivINT catalytic core domain - FIV
    • 4mq3 – FivINT catalytic core domain (mutant)
    • 5tc2 – HivINT C terminal – HIV-1
    • 5oi5, 5oi3, 5oi2 – HivINT catalytic core domain
    • 5jl4 – HivINT catalytic core domain (mutant)
    • 4nzg – INT N terminal – moloney murine leukemia virus
  • Integrase complex
    • [[2a3v – Rec INTI4+DNA – Vibrio cholera
    • [[1z19, 1z1b, 1z1g, 1p7d – EpLamInt catalytic core domain+DNA
    • [[1p4e, 1m6x – yFLP (mutant)+DNA – yeast
    • [[1flo - yFLP +DNA
    • 2wcc – INT DBD+ DNA – Enterobacteria phage - NMR
    • 5j0n – INT + ATTP + ATTB + integration host factor + excisionase - Cryo EM
    • 5m0r, 5m0q – VMvINT + DNA – Cryo EM
    • 6ex9, 5krt, 5krs, 5kgx, 5kgw, 4o0j – HivINT catalytic core domain + inhibitor
    • 5hrs, 5hrr, 5hrp, 5hrn, 5hot, 4tsx, 4ovl, 4ojr, 4o5b, 4o55, 4nyf – HivINT catalytic core domain (mutant) + inhibitor
    • 5eu7 – HivINT catalytic core domain + antibody
    • 4y1d, 4y1c – HivINT catalytic core domain + peptide
    • 6emy, 6emz, 6en0, 6en1, 6en2 – INT (mutant) + DNA – Enterococcus faecalis
    • 5uoq, 5uop, 5no1, 5mmb, 5mma, 5fro, 5frm, 4ztj, 4ztf – INT + DNA + inhibitor – human spumaretrovirus
    • 5ejk – INT + DNA + gag-pro-pol polyprotein – rous sarcoma virus

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PDBe, Michal Harel
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