P03367 (POL_HV1BR) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 172. History...
Names and origin
|Protein names||Recommended name:|
Cleaved into the following 11 chains:
|Organism||Human immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI) (HIV-1) [Complete proteome]|
|Taxonomic identifier||11686 [NCBI]|
|Taxonomic lineage||Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Lentivirus › Primate lentivirus group ›|
|Virus host||Homo sapiens (Human) [TaxID: 9606]|
|Sequence length||1447 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Gag-Pol polyprotein and Gag polyprotein may regulate their own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, Gag-Pol and Gag would promote translation, whereas at high concentration, the polyproteins encapsidate genomic RNA and then shutt off translation By similarity.
Matrix protein p17 has two main functions: in infected cell, it targets Gag and Gag-pol polyproteins to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. The second function is to play a role in nuclear localization of the viral genome at the very start of cell infection. Matrix protein is the part of the pre-integration complex. It binds in the cytoplasm the human BAF protein which prevent autointegration of the viral genome, and might be included in virions at the ration of zero to 3 BAF dimer per virion. The myristoylation signal and the NLS thus exert conflicting influences its subcellular localization. The key regulation of these motifs might be phosphorylation of a portion of MA molecules on the C-terminal tyrosine at the time of virus maturation, by virion-associated cellular tyrosine kinase. Implicated in the release from host cell mediated by Vpu By similarity.
Capsid protein p24 forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry. Interaction with human PPIA/CYPA protects the virus from restriction by human TRIM5-alpha and from an unknown antiviral activity in human cells. This capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species By similarity.
Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. Facilitates rearangement of nucleic acid secondary structure during retrotranscription of genomic RNA. This capability is referred to as nucleic acid chaperone activity By similarity.
The aspartyl protease mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response By similarity.
Reverse transcriptase/ribonuclease H (RT) is a multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends By similarity.
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 By similarity.
Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.
Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes: 1. sequence-specific internal cleavage of RNA. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end. 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus.
3'-end directed exonucleolytic cleavage of viral RNA-DNA hybrid.
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Binds 2 magnesium ions for reverse transcriptase polymerase activity By similarity.
Binds 2 magnesium ions for ribonuclease H (RNase H) activity. Substrate-binding is a precondition for magnesium binding By similarity.
Magnesium ions for integrase activity. Binds at least 1, maybe 2 magnesium ions By similarity.
The viral protease is inhibited by many synthetic protease inhibitors (PIs), such as amprenavir, atazanavir, indinavir, loprinavir, nelfinavir, ritonavir and saquinavir. RT can be inhibited either by nucleoside RT inhibitors (NRTIs) or by non nucleoside RT inhibitors (NNRTIs). NRTIs act as chain terminators, whereas NNRTIs inhibit DNA polymerization by binding a small hydrophobic pocket near the RT active site and inducing an allosteric change in this region. Classical NRTIs are abacavir, adefovir (PMEA), didanosine (ddI), lamivudine (3TC), stavudine (d4T), tenofovir (PMPA), zalcitabine (ddC), and zidovudine (AZT). Classical NNRTIs are atevirdine (BHAP U-87201E), delavirdine, efavirenz (DMP-266), emivirine (I-EBU), and nevirapine (BI-RG-587). The tritherapies used as a basic effective treatment of AIDS associate two NRTIs and one NNRTI. Use of protease inhibitors in tritherapy regimens permit more ambitious therapeutic strategies By similarity.
Pre-integration complex interacts with human HMGA1. Matrix protein p17 is a trimer. Interacts with gp120 and human BAF. Capsid is a homodimer. Interacts with human PPIA/CYPA. The protease is a homodimer, whose active site consists of two apposed aspartic acid residues. The reverse transcriptase is a heterodimer of p66 RT and p51 RT (RT p66/p51). Heterodimerization of RT is essential for DNA polymerase activity. Despite the sequence identities, p66 RT and p51 RT have distinct folding. Integrase is a homodimer and possibly can form homotetramer. Integrase interacts with human SMARCB1/INI1 and human PSIP1/LEDGF isoform 1Integrase interacts with human KPNA3; this interaction might play a role in nuclear import of the pre-integration complex. Integrase interacts with human NUP153; this interaction might play a role in nuclear import of the pre-integration complex By similarity.
Matrix protein p17: Virion Potential. Host nucleus By similarity. Host cytoplasm By similarity. Host cell membrane; Lipid-anchor Potential. Note: Following virus entry, the nuclear localization signal (NLS) of the matrix protein participates with Vpr to the nuclear localization of the viral genome. During virus production, the nuclear export activity of the matrix protein counteracts the NLS to maintain the Gag and Gag-Pol polyproteins in the cytoplasm, thereby directing unspliced RNA to the plasma membrane By similarity.
The reverse transcriptase/ribonuclease H (RT) is structured in five subdomains: finger, palm, thumb, connection and RNase H. Within the palm subdomain, the 'primer grip' region is thought to be involved in the positioning of the primer terminus for accommodating the incoming nucleotide. The RNase H domain stabilizes the association of RT with primer-template By similarity.
The tryptophan repeat motif is involved in RT p66/p51 dimerization By similarity.
Integrase core domain contains the D-x(n)-D-x(35)-E motif, named for the phylogenetically conserved glutamic acid and aspartic acid residues and the invariant 35 amino acid spacing between the second and third acidic residues. Each acidic residue of the D,D35E motif is independently essential for the 3'-processing and strand transfer activities of purified integrase protein By similarity.
Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation. Proteolytic cleavage of p66 RT removes the RNase H domain to yield the p51 RT subunit. Nucleocapsid protein p7 might be further cleaved after virus entry By similarity. Ref.3 Ref.4
Capsid protein p24 is phosphorylated By similarity.
Matrix protein p17 is tyrosine phosphorylated presumably in the virion by a host kinase. This modification targets the matrix protein to the nucleus By similarity.
Capsid protein p24 is able to bind macaque TRIM5-alpha or owl monkey TRIMCyp, preventing reverse transcription of the viral genome and succesfull infection of macaque or owl monkey by HIV-1 By similarity.
The reverse transcriptase is an error-prone enzyme that lacks a proof-reading function. High mutations rate is a direct consequence of this characteristic. RT also displays frequent template switching leading to high recombination rate. Recombination mostly occurs between homologous regions of the two copackaged RNA genomes. If these two RNA molecules derive from different viral strains, reverse transcription will give rise to highly recombinated proviral DNAs.
HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).
Resistance to inhibitors associated with mutations are observed both in viral protease and in reverse transcriptase. Most of the time, single mutations confer only a modest reduction in drug susceptibility. Combination of several mutations is usually required to develop a high-level drug resistance. These mutations are predominantly found in clade B viruses and not in other genotypes. They are listed in the clade B representative isolate HXB2 (AC P04585).
Contains 2 CCHC-type zinc fingers.
Contains 1 integrase catalytic domain.
Contains 1 integrase-type DNA-binding domain.
Contains 1 integrase-type zinc finger.
Contains 1 peptidase A2 domain.
Contains 1 reverse transcriptase domain.
Contains 1 RNase H domain.
|This entry describes 2 isoforms produced by ribosomal frameshifting. [Align] [Select]|
Note: Translation results in the formation of the Gag polyprotein most of the time. Ribosomal frameshifting at the gag-pol genes boundary occurs at low frequency and produces the Gag-Pol polyprotein. This strategy of translation probably allows the virus to modulate the quantity of each viral protein. Maintenance of a correct Gag to Gag-Pol ratio is essential for RNA dimerization and viral infectivity.
|Isoform Gag-Pol polyprotein (identifier: P03367-1) |
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
|Note: Produced by -1 ribosomal frameshifting.|
|Isoform Gag polyprotein (identifier: P03348-1) |
The sequence of this isoform can be found in the external entry P03348.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
|Note: Produced by conventional translation.|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed; by host By similarity|
|Chain||2 – 1447||1446||Gag-Pol polyprotein||PRO_0000261264|
|Chain||2 – 132||131||Matrix protein p17 By similarity||PRO_0000042330|
|Chain||133 – 363||231||Capsid protein p24 By similarity||PRO_0000042331|
|Peptide||364 – 377||14||Spacer peptide p2 By similarity||PRO_0000042332|
|Chain||378 – 432||55||Nucleocapsid protein p7 By similarity||PRO_0000042333|
|Peptide||433 – 440||8||Transframe peptide Potential||PRO_0000246712|
|Chain||441 – 500||60||p6-pol Potential||PRO_0000042334|
|Chain||501 – 599||99||Protease By similarity||PRO_0000038652|
|Chain||600 – 1159||560||Reverse transcriptase/ribonuclease H By similarity||PRO_0000042335|
|Chain||600 – 1039||440||p51 RT By similarity||PRO_0000042336|
|Chain||1040 – 1159||120||p15 By similarity||PRO_0000042337|
|Chain||1160 – 1447||288||Integrase By similarity||PRO_0000042338|
|Domain||520 – 589||70||Peptidase A2|
|Domain||643 – 833||191||Reverse transcriptase|
|Domain||1033 – 1156||124||RNase H|
|Domain||1213 – 1363||151||Integrase catalytic|
|Zinc finger||390 – 407||18||CCHC-type 1|
|Zinc finger||411 – 428||18||CCHC-type 2|
|Zinc finger||1162 – 1203||42||Integrase-type|
|DNA binding||1382 – 1429||48||Integrase-type|
|Region||826 – 834||9||RT 'primer grip' By similarity|
|Motif||16 – 22||7||Nuclear export signal By similarity|
|Motif||26 – 32||7||Nuclear localization signal By similarity|
|Motif||997 – 1013||17||Tryptophan repeat motif By similarity|
|Active site||525||1||For protease activity; shared with dimeric partner By similarity|
|Metal binding||709||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||784||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||785||1||Magnesium; catalytic; for reverse transcriptase activity By similarity|
|Metal binding||1042||1||Magnesium; catalytic; for RNase H activity By similarity|
|Metal binding||1077||1||Magnesium; catalytic; for RNase H activity By similarity|
|Metal binding||1097||1||Magnesium; catalytic; for RNase H activity By similarity|
|Metal binding||1148||1||Magnesium; catalytic; for RNase H activity By similarity|
|Metal binding||1223||1||Magnesium; catalytic; for integrase activity By similarity|
|Metal binding||1275||1||Magnesium; catalytic; for integrase activity By similarity|
|Site||132 – 133||2||Cleavage; by viral protease By similarity|
|Site||221 – 222||2||Cis/trans isomerization of proline peptide bond; by human PPIA/CYPA By similarity|
|Site||363 – 364||2||Cleavage; by viral protease By similarity|
|Site||377 – 378||2||Cleavage; by viral protease By similarity|
|Site||432 – 433||2||Cleavage; by viral protease Potential|
|Site||440 – 441||2||Cleavage; by viral protease By similarity|
|Site||500 – 501||2||Cleavage; by viral protease By similarity|
|Site||599 – 600||2||Cleavage; by viral protease By similarity|
|Site||1000||1||Essential for RT p66/p51 heterodimerization By similarity|
|Site||1013||1||Essential for RT p66/p51 heterodimerization By similarity|
|Site||1039 – 1040||2||Cleavage; by viral protease; partial By similarity|
|Site||1159 – 1160||2||Cleavage; by viral protease By similarity|
Amino acid modifications
|Modified residue||132||1||Phosphotyrosine; by host By similarity|
|Lipidation||2||1||N-myristoyl glycine; by host By similarity|
Helix Strand Turn
|Beta strand||502 – 504||3|
|Beta strand||505 – 507||3|
|Beta strand||510 – 515||6|
|Beta strand||518 – 524||7|
|Beta strand||529 – 533||5|
|Beta strand||542 – 549||8|
|Beta strand||552 – 566||15|
|Beta strand||569 – 578||10|
|Beta strand||581 – 585||5|
|Helix||587 – 590||4|
|Turn||591 – 594||4|
|Beta strand||596 – 598||3|
|Helix||627 – 642||16|
|Beta strand||645 – 648||4|
|Beta strand||659 – 663||5|
|Beta strand||668 – 674||7|
|Helix||677 – 682||6|
|Turn||697 – 701||5|
|Beta strand||702 – 709||8|
|Helix||711 – 716||6|
|Helix||721 – 724||4|
|Helix||725 – 727||3|
|Beta strand||729 – 731||3|
|Helix||734 – 736||3|
|Beta strand||741 – 747||7|
|Helix||754 – 758||5|
|Helix||760 – 773||14|
|Beta strand||777 – 782||6|
|Beta strand||785 – 790||6|
|Helix||794 – 809||16|
|Helix||828 – 830||3|
|Turn||835 – 837||3|
|Beta strand||849 – 852||4|
|Helix||853 – 866||14|
|Turn||867 – 869||3|
|Helix||876 – 881||6|
|Helix||896 – 909||14|
|Beta strand||926 – 928||3|
|Beta strand||935 – 945||11|
|Beta strand||947 – 954||8|
|Helix||963 – 982||20|
|Beta strand||987 – 992||6|
|Helix||994 – 1000||7|
|Helix||1001 – 1003||3|
|Beta strand||1012 – 1015||4|
|Helix||1020 – 1024||5|
|Beta strand||1352 – 1361||10|
|Helix||1370 – 1373||4|
|Turn||1374 – 1377||4|
|||"Nucleotide sequence of the AIDS virus, LAV."|
Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M.
Cell 40:9-17(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Genetic variability of the AIDS virus: nucleotide sequence analysis of two isolates from African patients."|
Alizon M., Wain-Hobson S., Montagnier L., Sonigo P.
Cell 46:63-74(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION TO 455-467.
|||"Cleavage of recombinant and cell derived human immunodeficiency virus 1 (HIV-1) Nef protein by HIV-1 protease."|
Gaedigk-Nitschko K., Schoen A., Wachinger G., Erfle V., Kohleisen B.
FEBS Lett. 357:275-278(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE OF NEF BY VIRAL PROTEASE.
|||"Intravirion processing of the human immunodeficiency virus type 1 Vif protein by the viral protease may be correlated with Vif function."|
Khan M.A., Akari H., Kao S., Aberham C., Davis D., Buckler-White A., Strebel K.
J. Virol. 76:9112-9123(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE OF VIF BY VIRAL PROTEASE.
|||"Proteolytic processing and particle maturation."|
Curr. Top. Microbiol. Immunol. 214:95-131(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"Structural biology of HIV."|
Turner B.G., Summers M.F.
J. Mol. Biol. 285:1-32(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"Mechanisms of retroviral recombination."|
Negroni M., Buc H.
Annu. Rev. Genet. 35:275-302(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
Dunn B.M., Goodenow M.M., Gustchina A., Wlodawer A.
Genome Biol. 3:REVIEWS3006.1-REVIEWS3006.7(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"Role of HIV-1 Gag domains in viral assembly."|
Scarlata S., Carter C.
Biochim. Biophys. Acta 1614:62-72(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"The three-dimensional structure of the aspartyl protease from the HIV-1 isolate BRU."|
Spinelli S., Liu Q.Z., Alzari P.M., Hirel P.H., Poljak R.J.
Biochimie 73:1391-1396(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 501-599.
|||"Structure of HIV-1 reverse transcriptase/DNA complex at 7 A resolution showing active site locations."|
Arnold E., Jacobo-Molina A., Nanni R.G., Williams R.L., Lu X., Ding J., Clark A.D. Jr., Zhang A., Ferris A.L., Clark P., Hizi A., Hughes S.H.
Nature 357:85-89(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 600-1026.
|||"Crystal structure at 1.9-A resolution of human immunodeficiency virus (HIV) II protease complexed with L-735,524, an orally bioavailable inhibitor of the HIV proteases."|
Chen Z., Li Y., Chen E., Hall D.L., Darke P.L., Culberson C., Shafer J.A., Kuo L.C.
J. Biol. Chem. 269:26344-26348(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 501-599 IN COMPLEX WITH THE INHIBITOR L-736,524.
|||"Structure-based design of HIV protease inhibitors: sulfonamide-containing 5,6-dihydro-4-hydroxy-2-pyrones as non-peptidic inhibitors."|
Thaisrivongs S., Skulnick H.I., Turner S.R., Strohbach J.W., Tommasi R.A., Johnson P.D., Aristoff P.A., Judge T.M., Gammill R.B., Morris J.K., Romines K.R., Chrusciel R.A., Hinshaw R.R., Chong K.-T., Tarpley W.G., Poppe S.M., Slade D.E., Lynn J.C. Watenpaugh K.D.
J. Med. Chem. 39:4349-4353(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 501-599.
|||"Inhibition and catalytic mechanism of HIV-1 aspartic protease."|
Silva A.M., Cachau R.E., Sham H.L., Erickson J.W.
J. Mol. Biol. 255:321-346(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 501-599 IN COMPLEX WITH THE DIFLUOROKETONE CONTAINING INHIBITOR A79285.
|||"Crystallographic analysis of human immunodeficiency virus 1 protease with an analog of the conserved CA-p2 substrate -- interactions with frequently occurring glutamic acid residue at P2' position of substrates."|
Weber I.T., Wu J., Adomat J.M., Harrison R.W., Kimmel A.R., Wondrak E.M., Louis J.M.
Eur. J. Biochem. 249:523-530(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 501-599.
|||"Structural basis for specificity of retroviral proteases."|
Wu J., Adomat J.M., Ridky T.W., Louis J.M., Leis J., Harrison R.W., Weber I.T.
Biochemistry 37:4518-4526(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 501-599.
|||"X-ray structure and conformational dynamics of the HIV-1 protease in complex with the inhibitor SDZ283-910: agreement of time-resolved spectroscopy and molecular dynamics simulations."|
Ringhofer S., Kallen J., Dutzler R., Billich A., Visser A.J., Scholz D., Steinhauser O., Schreiber H., Auer M., Kungl A.J.
J. Mol. Biol. 286:1147-1159(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 501-599 IN COMPLEX WITH INHIBITOR SDZ283-910.
|||"A distinct binding mode of a hydroxyethylamine isostere inhibitor of HIV-1 protease."|
Dohnalek J., Hasek J., Duskova J., Petrokova H., Hradilek M., Soucek M., Konvalinka J., Brynda J., Sedlacek J., Fabry M.
Acta Crystallogr. D 57:472-476(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 501-599 IN COMPLEX WITH A PEPTIDOMIMETIC INHIBITOR.
|||"Hydroxyethylamine isostere of an HIV-1 protease inhibitor prefers its amine to the hydroxy group in binding to catalytic aspartates. A synchrotron study of HIV-1 protease in complex with a peptidomimetic inhibitor."|
Dohnalek J., Hasek J., Duskova J., Petrokova H., Hradilek M., Soucek M., Konvalinka J., Brynda J., Sedlacek J., Fabry M.
J. Med. Chem. 45:1432-1438(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 501-599.
|||"An ethylenamine inhibitor binds tightly to both wild type and mutant HIV-1 proteases. Structure and energy study."|
Skalova T., Hasek J., Dohnalek J., Petrokova H., Buchtelova E., Duskova J., Soucek M., Majer P., Uhlikova T., Konvalinka J.
J. Med. Chem. 46:1636-1644(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 501-599 IN COMPLEX WITH AN ETHYLENAMINE PEPTIDOMIMETIC INHIBITOR.
|||"Role of hydroxyl group and R/S configuration of isostere in binding properties of HIV-1 protease inhibitors."|
Petrokova H., Duskova J., Dohnalek J., Skalova T., Vondrackova-Buchtelova E., Soucek M., Konvalinka J., Brynda J., Fabry M., Sedlacek J., Hasek J.
Eur. J. Biochem. 271:4451-4461(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 501-599 IN COMPLEX WITH AN ETHYLENEAMINE INHIBITOR.
|||"A structural and thermodynamic escape mechanism from a drug resistant mutation of the HIV-1 protease."|
Vega S., Kang L.W., Velazquez-Campoy A., Kiso Y., Amzel L.M., Freire E.
Proteins 55:594-602(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 501-599 IN COMPLEX WITH THE INHIBITOR KNI-577.
|||"A phenylnorstatine inhibitor binding to HIV-1 protease: geometry, protonation, and subsite-pocket interactions analyzed at atomic resolution."|
Brynda J., Rezacova P., Fabry M., Horejsi M., Stouracova R., Sedlacek J., Soucek M., Hradilek M., Lepsik M., Konvalinka J.
J. Med. Chem. 47:2030-2036(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.03 ANGSTROMS) OF 501-599 IN COMPLEX WITH A PEPTIDOMIMETIC INHIBITOR.
|||"High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains."|
Tie Y., Boross P.I., Wang Y.-F., Gaddis L., Hussain A.K., Leshchenko S., Ghosh A.K., Louis J.M., Harrison R.W., Weber I.T.
J. Mol. Biol. 338:341-352(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.1 ANGSTROMS) OF 501-599 IN COMPLEX WITH THE INHIBITOR UIC-94017.
|||"Crystal structures of HIV protease V82A and L90M mutants reveal changes in the indinavir-binding site."|
Mahalingam B., Wang Y.-F., Boross P.I., Tozser J., Louis J.M., Harrison R.W., Weber I.T.
Eur. J. Biochem. 271:1516-1524(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 501-599.
|||"Comparing the accumulation of active- and nonactive-site mutations in the HIV-1 protease."|
Clemente J.C., Moose R.E., Hemrajani R., Whitford L.R., Govindasamy L., Reutzel R., McKenna R., Agbandje-McKenna M., Goodenow M.M., Dunn B.M.
Biochemistry 43:12141-12151(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 501-599.
|||"Inhibitor binding at the protein interface in crystals of a HIV-1 protease complex."|
Brynda J., Rezacova P., Fabry M., Horejsi M., Stouracova R., Soucek M., Hradilek M., Konvalinka J., Sedlacek J.
Acta Crystallogr. D 60:1943-1948(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 501-599 IN COMPLEX WITH A PEPTIDOMIMETIC INHIBITOR.
|+||Additional computationally mapped references.|
|K02013 Genomic RNA. No translation available.|
3D structure databases
|SMR||P03367. Positions 1-432, 501-1156, 1160-1429. |
Protein-protein interaction databases
Protocols and materials databases
Family and domain databases
|Gene3D||126.96.36.199. 1 hit. |
1.10.1200.30. 1 hit.
188.8.131.52. 1 hit.
1.10.375.10. 1 hit.
184.108.40.206. 1 hit.
220.127.116.11. 1 hit.
3.30.420.10. 2 hits.
18.104.22.168. 1 hit.
|InterPro||IPR001969. Aspartic_peptidase_AS. |
|Pfam||PF00540. Gag_p17. 1 hit. |
PF00607. Gag_p24. 1 hit.
PF00552. IN_DBD_C. 1 hit.
PF02022. Integrase_Zn. 1 hit.
PF00075. RNase_H. 1 hit.
PF00665. rve. 1 hit.
PF00077. RVP. 1 hit.
PF00078. RVT_1. 1 hit.
PF06815. RVT_connect. 1 hit.
PF06817. RVT_thumb. 1 hit.
PF00098. zf-CCHC. 2 hits.
|PRINTS||PR00234. HIV1MATRIX. |
|SMART||SM00343. ZnF_C2HC. 2 hits. |
|SUPFAM||SSF46919. SSF46919. 1 hit. |
SSF47353. SSF47353. 1 hit.
SSF47836. SSF47836. 1 hit.
SSF47943. SSF47943. 1 hit.
SSF50122. SSF50122. 1 hit.
SSF50630. SSF50630. 1 hit.
SSF53098. SSF53098. 2 hits.
SSF57756. SSF57756. 1 hit.
|PROSITE||PS50175. ASP_PROT_RETROV. 1 hit. |
PS00141. ASP_PROTEASE. 1 hit.
PS50994. INTEGRASE. 1 hit.
PS51027. INTEGRASE_DBD. 1 hit.
PS50879. RNASE_H. 1 hit.
PS50878. RT_POL. 1 hit.
PS50158. ZF_CCHC. 2 hits.
PS50876. ZF_INTEGRASE. 1 hit.
|Accession||Primary (citable) accession number: P03367|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|