Gag-Pol polyprotein


Gag-Pol polyprotein
  • Pr160Gag-Pol
Gene Name
Amino acid sequence
>lcl|BSEQ0004048|Gag-Pol polyprotein
Number of residues
Molecular Weight
Theoretical pI
GO Classification
aspartic-type endopeptidase activity / DNA binding / DNA-directed DNA polymerase activity / exoribonuclease H activity / lipid binding / RNA binding / RNA-directed DNA polymerase activity / RNA-DNA hybrid ribonuclease activity / structural molecule activity / zinc ion binding
DNA integration / DNA recombination / establishment of integrated proviral latency / induction by virus of host cysteine-type endopeptidase activity involved in apoptotic process / suppression by virus of host gene expression / viral entry into host cell / viral penetration into host nucleus / viral release from host cell
host cell nucleus / host cell plasma membrane / host multivesicular body / viral nucleocapsid / virion membrane
General Function
Zinc ion binding
Specific Function
Gag-Pol polyprotein: Mediates, with Gag polyrotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shutt off translation.Matrix protein p17: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA.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 (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating. On the other hand, interactions with PDZD8 or CYPA stabilize the capsid.Nucleocapsid protein p7: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates to gRNA dimerization, packaging, tRNA incorporation and virion assembly.Protease: Aspartyl protease that 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: 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.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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Host cell membrane
Gene sequence
>lcl|BSEQ0004047|1539 bp
Chromosome Location
Not Available
Not Available
External Identifiers
UniProtKB IDP03366
UniProtKB Entry NamePOL_HV1B1
GenBank Protein ID326388
GenBank Gene IDM15654
General References
  1. Ratner L, Haseltine W, Patarca R, Livak KJ, Starcich B, Josephs SF, Doran ER, Rafalski JA, Whitehorn EA, Baumeister K, et al.: Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24-30;313(6000):277-84. [Article]
  2. Muesing MA, Smith DH, Cabradilla CD, Benton CV, Lasky LA, Capon DJ: Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus. Nature. 1985 Feb 7-13;313(6002):450-8. [Article]
  3. DeStefano JJ, Buiser RG, Mallaber LM, Bambara RA, Fay PJ: Human immunodeficiency virus reverse transcriptase displays a partially processive 3' to 5' endonuclease activity. J Biol Chem. 1991 Dec 25;266(36):24295-301. [Article]
  4. Jupp RA, Phylip LH, Mills JS, Le Grice SF, Kay J: Mutating P2 and P1 residues at cleavage junctions in the HIV-1 pol polyprotein. Effects on hydrolysis by HIV-1 proteinase. FEBS Lett. 1991 Jun 3;283(2):180-4. [Article]
  5. Wohrl BM, Volkmann S, Moelling K: Mutations of a conserved residue within HIV-1 ribonuclease H affect its exo- and endonuclease activities. J Mol Biol. 1991 Aug 5;220(3):801-18. [Article]
  6. Kaushik N, Rege N, Yadav PN, Sarafianos SG, Modak MJ, Pandey VN: Biochemical analysis of catalytically crucial aspartate mutants of human immunodeficiency virus type 1 reverse transcriptase. Biochemistry. 1996 Sep 10;35(36):11536-46. [Article]
  7. Palaniappan C, Wisniewski M, Jacques PS, Le Grice SF, Fay PJ, Bambara RA: Mutations within the primer grip region of HIV-1 reverse transcriptase result in loss of RNase H function. J Biol Chem. 1997 Apr 25;272(17):11157-64. [Article]
  8. Gao HQ, Boyer PL, Arnold E, Hughes SH: Effects of mutations in the polymerase domain on the polymerase, RNase H and strand transfer activities of human immunodeficiency virus type 1 reverse transcriptase. J Mol Biol. 1998 Apr 3;277(3):559-72. [Article]
  9. Harris D, Yadav PN, Pandey VN: Loss of polymerase activity due to Tyr to Phe substitution in the YMDD motif of human immunodeficiency virus type-1 reverse transcriptase is compensated by Met to Val substitution within the same motif. Biochemistry. 1998 Jul 7;37(27):9630-40. [Article]
  10. Smith CM, Leon O, Smith JS, Roth MJ: Sequence requirements for removal of tRNA by an isolated human immunodeficiency virus type 1 RNase H domain. J Virol. 1998 Aug;72(8):6805-12. [Article]
  11. Sluis-Cremer N, Arion D, Kaushik N, Lim H, Parniak MA: Mutational analysis of Lys65 of HIV-1 reverse transcriptase. Biochem J. 2000 May 15;348 Pt 1:77-82. [Article]
  12. Wisniewski M, Balakrishnan M, Palaniappan C, Fay PJ, Bambara RA: Unique progressive cleavage mechanism of HIV reverse transcriptase RNase H. Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):11978-83. [Article]
  13. Chen N, Morag A, Almog N, Blumenzweig I, Dreazin O, Kotler M: Extended nucleocapsid protein is cleaved from the Gag-Pol precursor of human immunodeficiency virus type 1. J Gen Virol. 2001 Mar;82(Pt 3):581-90. [Article]
  14. Shehu-Xhilaga M, Crowe SM, Mak J: Maintenance of the Gag/Gag-Pol ratio is important for human immunodeficiency virus type 1 RNA dimerization and viral infectivity. J Virol. 2001 Feb;75(4):1834-41. [Article]
  15. Koval'skii DB, Kanibolotskii DS, Dubina VN, Korneliuk AI: [Conformational changes in HIV-1 proteinase: effect of protonation of the active center on conformation of HIV-1 proteinase in water]. Ukr Biokhim Zh (1999). 2002 Nov-Dec;74(6):135-8. [Article]
  16. Sharma B, Kaushik N, Singh K, Kumar S, Pandey VN: Substitution of conserved hydrophobic residues in motifs B and C of HIV-1 RT alters the geometry of its catalytic pocket. Biochemistry. 2002 Dec 31;41(52):15685-97. [Article]
  17. Arion D, Sluis-Cremer N, Min KL, Abram ME, Fletcher RS, Parniak MA: Mutational analysis of Tyr-501 of HIV-1 reverse transcriptase. Effects on ribonuclease H activity and inhibition of this activity by N-acylhydrazones. J Biol Chem. 2002 Jan 11;277(2):1370-4. Epub 2001 Oct 29. [Article]
  18. Tachedjian G, Aronson HE, de los Santos M, Seehra J, McCoy JM, Goff SP: Role of residues in the tryptophan repeat motif for HIV-1 reverse transcriptase dimerization. J Mol Biol. 2003 Feb 14;326(2):381-96. [Article]
  19. Schultz SJ, Zhang M, Champoux JJ: Recognition of internal cleavage sites by retroviral RNases H. J Mol Biol. 2004 Nov 26;344(3):635-52. [Article]
  20. Tachedjian G, Radzio J, Sluis-Cremer N: Relationship between enzyme activity and dimeric structure of recombinant HIV-1 reverse transcriptase. Proteins. 2005 Jul 1;60(1):5-13. [Article]
  21. Mulder BA, Anaya S, Yu P, Lee KW, Nguyen A, Murphy J, Willson R, Briggs JM, Gao X, Hardin SH: Nucleotide modification at the gamma-phosphate leads to the improved fidelity of HIV-1 reverse transcriptase. Nucleic Acids Res. 2005 Sep 1;33(15):4865-73. Print 2005. [Article]
  22. Abram ME, Parniak MA: Virion instability of human immunodeficiency virus type 1 reverse transcriptase (RT) mutated in the protease cleavage site between RT p51 and the RT RNase H domain. J Virol. 2005 Sep;79(18):11952-61. [Article]
  23. Invernizzi CF, Xie B, Frankel FA, Feldhammer M, Roy BB, Richard S, Wainberg MA: Arginine methylation of the HIV-1 nucleocapsid protein results in its diminished function. AIDS. 2007 Apr 23;21(7):795-805. [Article]
  24. Vogt VM: Proteolytic processing and particle maturation. Curr Top Microbiol Immunol. 1996;214:95-131. [Article]
  25. Turner BG, Summers MF: Structural biology of HIV. J Mol Biol. 1999 Jan 8;285(1):1-32. [Article]
  26. Negroni M, Buc H: Mechanisms of retroviral recombination. Annu Rev Genet. 2001;35:275-302. [Article]
  27. Dunn BM, Goodenow MM, Gustchina A, Wlodawer A: Retroviral proteases. Genome Biol. 2002;3(4):REVIEWS3006. Epub 2002 Mar 26. [Article]
  28. Scarlata S, Carter C: Role of HIV-1 Gag domains in viral assembly. Biochim Biophys Acta. 2003 Jul 11;1614(1):62-72. [Article]
  29. Weber IT, Miller M, Jaskolski M, Leis J, Skalka AM, Wlodawer A: Molecular modeling of the HIV-1 protease and its substrate binding site. Science. 1989 Feb 17;243(4893):928-31. [Article]
  30. Mizrahi V, Lazarus GM, Miles LM, Meyers CA, Debouck C: Recombinant HIV-1 reverse transcriptase: purification, primary structure, and polymerase/ribonuclease H activities. Arch Biochem Biophys. 1989 Sep;273(2):347-58. [Article]
  31. Erickson J, Neidhart DJ, VanDrie J, Kempf DJ, Wang XC, Norbeck DW, Plattner JJ, Rittenhouse JW, Turon M, Wideburg N, et al.: Design, activity, and 2.8 A crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease. Science. 1990 Aug 3;249(4968):527-33. [Article]
  32. Davies JF 2nd, Hostomska Z, Hostomsky Z, Jordan SR, Matthews DA: Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase. Science. 1991 Apr 5;252(5002):88-95. [Article]
  33. Evans DB, Brawn K, Deibel MR Jr, Tarpley WG, Sharma SK: A recombinant ribonuclease H domain of HIV-1 reverse transcriptase that is enzymatically active. J Biol Chem. 1991 Nov 5;266(31):20583-5. [Article]
  34. Hostomska Z, Matthews DA, Davies JF 2nd, Nodes BR, Hostomsky Z: Proteolytic release and crystallization of the RNase H domain of human immunodeficiency virus type 1 reverse transcriptase. J Biol Chem. 1991 Aug 5;266(22):14697-702. [Article]
  35. Kohlstaedt LA, Wang J, Friedman JM, Rice PA, Steitz TA: Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science. 1992 Jun 26;256(5065):1783-90. [Article]
  36. Arnold E, Jacobo-Molina A, Nanni RG, Williams RL, Lu X, Ding J, Clark AD Jr, Zhang A, Ferris AL, Clark P, et al.: Structure of HIV-1 reverse transcriptase/DNA complex at 7 A resolution showing active site locations. Nature. 1992 May 7;357(6373):85-9. [Article]
  37. Wonacott A, Cooke R, Hayes FR, Hann MM, Jhoti H, McMeekin P, Mistry A, Murray-Rust P, Singh OM, Weir MP: A series of penicillin-derived C2-symmetric inhibitors of HIV-1 proteinase: structural and modeling studies. J Med Chem. 1993 Oct 15;36(21):3113-9. [Article]
  38. Newlander KA, Callahan JF, Moore ML, Tomaszek TA Jr, Huffman WF: A novel constrained reduced-amide inhibitor of HIV-1 protease derived from the sequential incorporation of gamma-turn mimetics into a model substrate. J Med Chem. 1993 Aug 6;36(16):2321-31. [Article]
  39. Jacobo-Molina A, Ding J, Nanni RG, Clark AD Jr, Lu X, Tantillo C, Williams RL, Kamer G, Ferris AL, Clark P, et al.: Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 A resolution shows bent DNA. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6320-4. [Article]
  40. Smerdon SJ, Jager J, Wang J, Kohlstaedt LA, Chirino AJ, Friedman JM, Rice PA, Steitz TA: Structure of the binding site for nonnucleoside inhibitors of the reverse transcriptase of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3911-5. [Article]
  41. Priestle JP, Fassler A, Rosel J, Tintelnot-Blomley M, Strop P, Grutter MG: Comparative analysis of the X-ray structures of HIV-1 and HIV-2 proteases in complex with CGP 53820, a novel pseudosymmetric inhibitor. Structure. 1995 Apr 15;3(4):381-9. [Article]
  42. Ding J, Das K, Moereels H, Koymans L, Andries K, Janssen PA, Hughes SH, Arnold E: Structure of HIV-1 RT/TIBO R 86183 complex reveals similarity in the binding of diverse nonnucleoside inhibitors. Nat Struct Biol. 1995 May;2(5):407-15. [Article]
  43. Ding J, Das K, Tantillo C, Zhang W, Clark AD Jr, Jessen S, Lu X, Hsiou Y, Jacobo-Molina A, Andries K, et al.: Structure of HIV-1 reverse transcriptase in a complex with the non-nucleoside inhibitor alpha-APA R 95845 at 2.8 A resolution. Structure. 1995 Apr 15;3(4):365-79. [Article]
  44. Rodgers DW, Gamblin SJ, Harris BA, Ray S, Culp JS, Hellmig B, Woolf DJ, Debouck C, Harrison SC: The structure of unliganded reverse transcriptase from the human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1222-6. [Article]
  45. Eijkelenboom AP, Lutzke RA, Boelens R, Plasterk RH, Kaptein R, Hard K: The DNA-binding domain of HIV-1 integrase has an SH3-like fold. Nat Struct Biol. 1995 Sep;2(9):807-10. [Article]
  46. Lin Y, Lin X, Hong L, Foundling S, Heinrikson RL, Thaisrivongs S, Leelamanit W, Raterman D, Shah M, Dunn BM, et al.: Effect of point mutations on the kinetics and the inhibition of human immunodeficiency virus type 1 protease: relationship to drug resistance. Biochemistry. 1995 Jan 31;34(4):1143-52. [Article]
  47. Hsiou Y, Ding J, Das K, Clark AD Jr, Hughes SH, Arnold E: Structure of unliganded HIV-1 reverse transcriptase at 2.7 A resolution: implications of conformational changes for polymerization and inhibition mechanisms. Structure. 1996 Jul 15;4(7):853-60. [Article]
  48. Backbro K, Lowgren S, Osterlund K, Atepo J, Unge T, Hulten J, Bonham NM, Schaal W, Karlen A, Hallberg A: Unexpected binding mode of a cyclic sulfamide HIV-1 protease inhibitor. J Med Chem. 1997 Mar 14;40(6):898-902. [Article]
  49. Ala PJ, Huston EE, Klabe RM, McCabe DD, Duke JL, Rizzo CJ, Korant BD, DeLoskey RJ, Lam PY, Hodge CN, Chang CH: Molecular basis of HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with cyclic urea inhibitors. Biochemistry. 1997 Feb 18;36(7):1573-80. [Article]
  50. Hong L, Zhang XJ, Foundling S, Hartsuck JA, Tang J: Structure of a G48H mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs. FEBS Lett. 1997 Dec 22;420(1):11-6. [Article]
  51. Smith AB 3rd, Hirschmann R, Pasternak A, Yao W, Sprengeler PA, Holloway MK, Kuo LC, Chen Z, Darke PL, Schleif WA: An orally bioavailable pyrrolinone inhibitor of HIV-1 protease: computational analysis and X-ray crystal structure of the enzyme complex. J Med Chem. 1997 Aug 1;40(16):2440-4. [Article]
  52. Hong L, Hartsuck JA, Foundling S, Ermolieff J, Tang J: Active-site mobility in human immunodeficiency virus, type 1, protease as demonstrated by crystal structure of A28S mutant. Protein Sci. 1998 Feb;7(2):300-5. [Article]
  53. Huang H, Chopra R, Verdine GL, Harrison SC: Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science. 1998 Nov 27;282(5394):1669-75. [Article]
  54. Jaeger J, Restle T, Steitz TA: The structure of HIV-1 reverse transcriptase complexed with an RNA pseudoknot inhibitor. EMBO J. 1998 Aug 3;17(15):4535-42. [Article]
  55. Hsiou Y, Das K, Ding J, Clark AD Jr, Kleim JP, Rosner M, Winkler I, Riess G, Hughes SH, Arnold E: Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance. J Mol Biol. 1998 Nov 27;284(2):313-23. [Article]
  56. Sarafianos SG, Das K, Clark AD Jr, Ding J, Boyer PL, Hughes SH, Arnold E: Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids. Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10027-32. [Article]
  57. Hogberg M, Sahlberg C, Engelhardt P, Noreen R, Kangasmetsa J, Johansson NG, Oberg B, Vrang L, Zhang H, Sahlberg BL, Unge T, Lovgren S, Fridborg K, Backbro K: Urea-PETT compounds as a new class of HIV-1 reverse transcriptase inhibitors. 3. Synthesis and further structure-activity relationship studies of PETT analogues J Med Chem. 2000 Jan 27;43(2):304. [Article]
  58. Sarafianos SG, Das K, Tantillo C, Clark AD Jr, Ding J, Whitcomb JM, Boyer PL, Hughes SH, Arnold E: Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA. EMBO J. 2001 Mar 15;20(6):1449-61. [Article]
  59. Hsiou Y, Ding J, Das K, Clark AD Jr, Boyer PL, Lewi P, Janssen PA, Kleim JP, Rosner M, Hughes SH, Arnold E: The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. J Mol Biol. 2001 Jun 1;309(2):437-45. [Article]
  60. Sarafianos SG, Clark AD Jr, Das K, Tuske S, Birktoft JJ, Ilankumaran P, Ramesha AR, Sayer JM, Jerina DM, Boyer PL, Hughes SH, Arnold E: Structures of HIV-1 reverse transcriptase with pre- and post-translocation AZTMP-terminated DNA. EMBO J. 2002 Dec 2;21(23):6614-24. [Article]
  61. Lindberg J, Sigurdsson S, Lowgren S, Andersson HO, Sahlberg C, Noreen R, Fridborg K, Zhang H, Unge T: Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 towards the HIV-1 RT K103N mutant. Eur J Biochem. 2002 Mar;269(6):1670-7. [Article]
  62. Andersson HO, Fridborg K, Lowgren S, Alterman M, Muhlman A, Bjorsne M, Garg N, Kvarnstrom I, Schaal W, Classon B, Karlen A, Danielsson UH, Ahlsen G, Nillroth U, Vrang L, Oberg B, Samuelsson B, Hallberg A, Unge T: Optimization of P1-P3 groups in symmetric and asymmetric HIV-1 protease inhibitors. Eur J Biochem. 2003 Apr;270(8):1746-58. [Article]
  63. Smith AB 3rd, Cantin LD, Pasternak A, Guise-Zawacki L, Yao W, Charnley AK, Barbosa J, Sprengeler PA, Hirschmann R, Munshi S, Olsen DB, Schleif WA, Kuo LC: Design, synthesis, and biological evaluation of monopyrrolinone-based HIV-1 protease inhibitors. J Med Chem. 2003 May 8;46(10):1831-44. [Article]
  64. Lindberg J, Pyring D, Lowgren S, Rosenquist A, Zuccarello G, Kvarnstrom I, Zhang H, Vrang L, Classon B, Hallberg A, Samuelsson B, Unge T: Symmetric fluoro-substituted diol-based HIV protease inhibitors. Ortho-fluorinated and meta-fluorinated P1/P1'-benzyloxy side groups significantly improve the antiviral activity and preserve binding efficacy. Eur J Biochem. 2004 Nov;271(22):4594-602. [Article]
  65. Peletskaya EN, Kogon AA, Tuske S, Arnold E, Hughes SH: Nonnucleoside inhibitor binding affects the interactions of the fingers subdomain of human immunodeficiency virus type 1 reverse transcriptase with DNA. J Virol. 2004 Apr;78(7):3387-97. [Article]
  66. Tuske S, Sarafianos SG, Clark AD Jr, Ding J, Naeger LK, White KL, Miller MD, Gibbs CS, Boyer PL, Clark P, Wang G, Gaffney BL, Jones RA, Jerina DM, Hughes SH, Arnold E: Structures of HIV-1 RT-DNA complexes before and after incorporation of the anti-AIDS drug tenofovir. Nat Struct Mol Biol. 2004 May;11(5):469-74. Epub 2004 Apr 25. [Article]
  67. Huang PP, Randolph JT, Klein LL, Vasavanonda S, Dekhtyar T, Stoll VS, Kempf DJ: Synthesis and antiviral activity of P1' arylsulfonamide azacyclic urea HIV protease inhibitors. Bioorg Med Chem Lett. 2004 Aug 2;14(15):4075-8. [Article]
  68. Yeung CM, Klein LL, Flentge CA, Randolph JT, Zhao C, Sun M, Dekhtyar T, Stoll VS, Kempf DJ: Oximinoarylsulfonamides as potent HIV protease inhibitors. Bioorg Med Chem Lett. 2005 May 2;15(9):2275-8. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01732(4R,5S,6S,7R)-1,3-dibenzyl-4,7-bis(phenoxymethyl)-5,6-dihydroxy-1,3 diazepan-2-oneexperimentalunknownDetails
DB01824(3S)-Tetrahydro-3-furanyl {(2S,3S)-4-[(2S,4R)-4-{(1S,2R)-2-[(S)-amino(hydroxy)methoxy]-2,3-dihydro-1H-inden-1-yl}-2-benzyl-3-oxo-2-pyrrolidinyl]-3-hydroxy-1-phenyl-2-butanyl}carbamateexperimentalunknownDetails
DB02683Inhibitor Bea428experimentalunknownDetails
DB02768Tert-Butyloxycarbonyl GroupexperimentalunknownDetails
DB02785(2S)-1-[(2S,4R)-4-Benzyl-2-hydroxy-5-{[(1S,2R,5S)-2-hydroxy-5-methylcyclopentyl]amino}-5-oxopentyl]-4-{[6-chloro-5-(4-methyl-1-piperazinyl)-2-pyrazinyl]carbonyl}-N-(2-methyl-2-propanyl)-2-piperazineca rboxamideexperimentalunknownDetails
DB041902,5-dibenzyloxy-3-hydroxy-hexanedioic acid bis-[(2-hydroxy-indan-1-yl)-amide]experimentalunknownDetails
DB04255Inhibitor BEA388experimentalunknownDetails
DB04547Inhibitor BEA409experimentalunknownDetails
DB08281O-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl] (4-bromophenyl)thiocarbamateexperimentalunknownDetails
DB08282O-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl] (4-chlorophenyl)thiocarbamateexperimentalunknownDetails
DB08284O-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl] (4-iodophenyl)thiocarbamateexperimentalunknownDetails