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PDBsum entry 1rtj
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protein Protein-protein interface(s) links
Nucleotidyltransferase PDB id
1rtj

 

 

 

 

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Contents
Protein chains
543 a.a. *
426 a.a. *
Waters ×267
* Residue conservation analysis
PDB id:
1rtj
Name: Nucleotidyltransferase
Title: Mechanism of inhibition of HIV-1 reverse transcriptase by non- nucleoside inhibitors
Structure: HIV-1 reverse transcriptase. Chain: a. Synonym: HIV-1 rt. Engineered: yes. HIV-1 reverse transcriptase. Chain: b. Synonym: HIV-1 rt. Engineered: yes
Source: Human immunodeficiency virus 1. Organism_taxid: 11676. Strain: hxb2 isolate. Cell_line: 293. Gene: HIV-1 pol. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.35Å     R-factor:   0.219    
Authors: J.Ren,R.Esnouf,C.Ross,Y.Jones,D.Stammers,D.Stuart
Key ref: R.Esnouf et al. (1995). Mechanism of inhibition of HIV-1 reverse transcriptase by non-nucleoside inhibitors. Nat Struct Biol, 2, 303-308. PubMed id: 7540935
Date:
03-May-95     Release date:   03-Apr-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P04585  (POL_HV1H2) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1435 a.a.
543 a.a.*
Protein chain
Pfam   ArchSchema ?
P04585  (POL_HV1H2) -  Gag-Pol polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1435 a.a.
426 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 1: Chains A, B: E.C.2.7.7.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
   Enzyme class 2: Chains A, B: E.C.2.7.7.49  - RNA-directed Dna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
DNA(n)
 + 2'-deoxyribonucleoside 5'-triphosphate
 = DNA(n+1)
 + diphosphate
   Enzyme class 3: Chains A, B: E.C.2.7.7.7  - DNA-directed Dna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
DNA(n)
 + 2'-deoxyribonucleoside 5'-triphosphate
 = DNA(n+1)
 + diphosphate
   Enzyme class 4: Chains A, B: E.C.3.1.-.-
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
   Enzyme class 5: Chains A, B: E.C.3.1.13.2  - exoribonuclease H.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Exonucleolytic cleavage to 5'-phosphomonoester oligonucleotides in both 5'- to 3'- and 3'- to 5'-directions.
   Enzyme class 6: Chains A, B: E.C.3.1.26.13  - retroviral ribonuclease H.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
   Enzyme class 7: Chains A, B: E.C.3.4.23.16  - HIV-1 retropepsin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      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

 

 
    reference    
 
 
Nat Struct Biol 2:303-308 (1995)
PubMed id: 7540935  
 
 
Mechanism of inhibition of HIV-1 reverse transcriptase by non-nucleoside inhibitors.
R.Esnouf, J.Ren, C.Ross, Y.Jones, D.Stammers, D.Stuart.
 
  ABSTRACT  
 
The structure of unliganded HIV-1 reverse transcriptase has been determined at 2.35 A resolution and refined to an R-factor of 0.219 (for all data) with good stereochemistry. The unliganded structure was produced by soaking out a weak binding non-nucleoside inhibitor, HEPT, from pregrown crystals. Comparison with the structures of four different RT and non-nucleoside inhibitor complexes reveals that only minor domain rearrangements occur, but there is a significant repositioning of a three-stranded beta-sheet in the p66 subunit (containing the catalytic aspartic acid residues 110, 185 and 186) with respect to the rest of the polymerase site. This suggests that NNIs inhibit RT by locking the polymerase active site in an inactive conformation, reminiscent of the conformation observed in the inactive p51 subunit.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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  ChemMedChem, 6, 228-241.  
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  Future Microbiol, 6, 295-315.  
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  20011151 A.J.Kandathil, A.P.Joseph, R.Kannangai, N.Srinivasan, O.C.Abraham, S.A.Pulimood, and G.Sridharan (2010).
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PDB code: 1tv6
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  J Virol, 78, 5390-5401.  
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HIV resistance to nevirapine and other non-nucleoside reverse transcriptase inhibitors.
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PDB code: 1o5s
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PDB codes: 1ikv 1ikw 1ikx 1iky
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Structure of HIV-2 reverse transcriptase at 2.35-A resolution and the mechanism of resistance to non-nucleoside inhibitors.
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PDB code: 1mu2
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Genotypic testing for human immunodeficiency virus type 1 drug resistance.
  Clin Microbiol Rev, 15, 247-277.  
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Mutagenesis of key residues identifies the connection subdomain of HIV-1 reverse transcriptase as the site of inhibition by heme.
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Molecular dynamics of HIV-1 reverse transcriptase indicates increased flexibility upon DNA binding.
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HIV drug resistance and implications for the introduction of antiretroviral therapy in resource-poor countries.
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Non-nucleoside reverse transcriptase inhibitors: perspectives on novel therapeutic compounds and strategies for the treatment of HIV infection.
  Expert Opin Investig Drugs, 10, 1423-1442.  
10770750 G.Maga, D.Ubiali, R.Salvetti, M.Pregnolato, and S.Spadari (2000).
Selective interaction of the human immunodeficiency virus type 1 reverse transcriptase nonnucleoside inhibitor efavirenz and its thio-substituted analog with different enzyme-substrate complexes.
  Antimicrob Agents Chemother, 44, 1186-1194.  
10841542 G.Tachedjian, H.E.Aronson, and S.P.Goff (2000).
Analysis of mutations and suppressors affecting interactions between the subunits of the HIV type 1 reverse transcriptase.
  Proc Natl Acad Sci U S A, 97, 6334-6339.  
10708278 H.Salomon, M.A.Wainberg, B.Brenner, Y.Quan, D.Rouleau, P.Coté, R.LeBlanc, E.Lefebvre, B.Spira, C.Tsoukas, R.P.Sekaly, B.Conway, D.Mayers, and J.P.Routy (2000).
Prevalence of HIV-1 resistant to antiretroviral drugs in 81 individuals newly infected by sexual contact or injecting drug use. Investigators of the Quebec Primary Infection Study.
  AIDS, 14, F17-F23.  
10681506 J.J.Arnold, and C.E.Cameron (2000).
Poliovirus RNA-dependent RNA polymerase (3D(pol)). Assembly of stable, elongation-competent complexes by using a symmetrical primer-template substrate (sym/sub).
  J Biol Chem, 275, 5329-5336.  
10799511 J.Ren, C.Nichols, L.E.Bird, T.Fujiwara, H.Sugimoto, D.I.Stuart, and D.K.Stammers (2000).
Binding of the second generation non-nucleoside inhibitor S-1153 to HIV-1 reverse transcriptase involves extensive main chain hydrogen bonding.
  J Biol Chem, 275, 14316-14320.
PDB code: 1ep4
10681546 J.Ren, J.Diprose, J.Warren, R.M.Esnouf, L.E.Bird, S.Ikemizu, M.Slater, J.Milton, J.Balzarini, D.I.Stuart, and D.K.Stammers (2000).
Phenylethylthiazolylthiourea (PETT) non-nucleoside inhibitors of HIV-1 and HIV-2 reverse transcriptases. Structural and biochemical analyses.
  J Biol Chem, 275, 5633-5639.
PDB codes: 1dtq 1dtt
11080630 J.Ren, J.Milton, K.L.Weaver, S.A.Short, D.I.Stuart, and D.K.Stammers (2000).
Structural basis for the resilience of efavirenz (DMP-266) to drug resistance mutations in HIV-1 reverse transcriptase.
  Structure, 8, 1089-1094.
PDB codes: 1fk9 1fko 1fkp
10673109 J.W.Corbett, L.A.Gearhart, S.S.Ko, J.D.Rodgers, B.C.Cordova, R.M.Klabe, and S.K.Erickson-Viitanen (2000).
Novel 2,2-dioxide-4,4-disubstituted-1,3-H-2,1,3-benzothiadiazines as non-nucleoside reverse transcriptase inhibitors.
  Bioorg Med Chem Lett, 10, 193-195.  
10954539 R.H.Archer, C.Dykes, P.Gerondelis, A.Lloyd, P.Fay, R.C.Reichman, R.A.Bambara, and L.M.Demeter (2000).
Mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors demonstrate altered rates of RNase H cleavage that correlate with HIV-1 replication fitness in cell culture.
  J Virol, 74, 8390-8401.  
  19096725 R.W.Shafer, R.Kantor, and M.J.Gonzales (2000).
The Genetic Basis of HIV-1 Resistance to Reverse Transcriptase and Protease Inhibitors.
  AIDS Rev, 2, 211-228.  
10585459 B.Canard, K.Chowdhury, R.Sarfati, S.Doublié, and C.C.Richardson (1999).
The motif D loop of human immunodeficiency virus type 1 reverse transcriptase is critical for nucleoside 5'-triphosphate selectivity.
  J Biol Chem, 274, 35768-35776.  
10022845 C.Isel, E.Westhof, C.Massire, S.F.Le Grice, B.Ehresmann, C.Ehresmann, and R.Marquet (1999).
Structural basis for the specificity of the initiation of HIV-1 reverse transcription.
  EMBO J, 18, 1038-1048.  
9880532 E.G.Argyris, J.M.Vanderkooi, P.S.Venkateswaran, B.K.Kay, and Y.Paterson (1999).
The connection domain is implicated in metalloporphyrin binding and inhibition of HIV reverse transcriptase.
  J Biol Chem, 274, 1549-1556.  
10047577 J.Jäger, and J.D.Pata (1999).
Getting a grip: polymerases and their substrate complexes.
  Curr Opin Struct Biol, 9, 21-28.  
  10582878 J.W.Corbett, S.S.Ko, J.D.Rodgers, S.Jeffrey, L.T.Bacheler, R.M.Klabe, S.Diamond, C.M.Lai, S.R.Rabel, J.A.Saye, S.P.Adams, G.L.Trainor, P.S.Anderson, and S.K.Erickson-Viitanen (1999).
Expanded-spectrum nonnucleoside reverse transcriptase inhibitors inhibit clinically relevant mutant variants of human immunodeficiency virus type 1.
  Antimicrob Agents Chemother, 43, 2893-2897.  
10563792 M.C.Morris, C.Berducou, J.Mery, F.Heitz, and G.Divita (1999).
The thumb domain of the P51-subunit is essential for activation of HIV reverse transcriptase.
  Biochemistry, 38, 15097-15103.  
10455170 M.C.Morris, V.Robert-Hebmann, L.Chaloin, J.Mery, F.Heitz, C.Devaux, R.S.Goody, and G.Divita (1999).
A new potent HIV-1 reverse transcriptase inhibitor. A synthetic peptide derived from the interface subunit domains.
  J Biol Chem, 274, 24941-24946.  
  10364332 P.Gerondelis, R.H.Archer, C.Palaniappan, R.C.Reichman, P.J.Fay, R.A.Bambara, and L.M.Demeter (1999).
The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities.
  J Virol, 73, 5803-5813.  
10468556 S.G.Sarafianos, K.Das, A.D.Clark, J.Ding, P.L.Boyer, S.H.Hughes, and E.Arnold (1999).
Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids.
  Proc Natl Acad Sci U S A, 96, 10027-10032.
PDB codes: 1c9r 1j5o 1qe1
10322129 S.G.Sarafianos, K.Das, J.Ding, P.L.Boyer, S.H.Hughes, and E.Arnold (1999).
Touching the heart of HIV-1 drug resistance: the fingers close down on the dNTP at the polymerase active site.
  Chem Biol, 6, R137-R146.  
10368306 T.Darden, L.Perera, L.Li, and L.Pedersen (1999).
New tricks for modelers from the crystallography toolkit: the particle mesh Ewald algorithm and its use in nucleic acid simulations.
  Structure, 7, R55-R60.  
9759480 A.D.Frankel, and J.A.Young (1998).
HIV-1: fifteen proteins and an RNA.
  Annu Rev Biochem, 67, 1.  
  9684890 D.Sun, S.Jessen, C.Liu, X.Liu, S.Najmudin, and M.M.Georgiadis (1998).
Cloning, expression, and purification of a catalytic fragment of Moloney murine leukemia virus reverse transcriptase: crystallization of nucleic acid complexes.
  Protein Sci, 7, 1575-1582.  
9754886 E.De Clercq (1998).
The role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the therapy of HIV-1 infection.
  Antiviral Res, 38, 153-179.  
9852086 H.Pelemans, R.M.Esnouf, H.Jonckheere, E.De Clercq, and J.Balzarini (1998).
Mutational analysis of Tyr-318 within the non-nucleoside reverse transcriptase inhibitor binding pocket of human immunodeficiency virus type I reverse transcriptase.
  J Biol Chem, 273, 34234-34239.  
9435245 J.A.Wrobel, S.F.Chao, M.J.Conrad, J.D.Merker, R.Swanstrom, G.J.Pielak, and C.A.Hutchison (1998).
A genetic approach for identifying critical residues in the fingers and palm subdomains of HIV-1 reverse transcriptase.
  Proc Natl Acad Sci U S A, 95, 638-645.  
9733733 J.M.Lanchy, G.Keith, S.F.Le Grice, B.Ehresmann, C.Ehresmann, and R.Marquet (1998).
Contacts between reverse transcriptase and the primer strand govern the transition from initiation to elongation of HIV-1 reverse transcription.
  J Biol Chem, 273, 24425-24432.  
9689112 J.Ren, R.M.Esnouf, A.L.Hopkins, E.Y.Jones, I.Kirby, J.Keeling, C.K.Ross, B.A.Larder, D.I.Stuart, and D.K.Stammers (1998).
3'-Azido-3'-deoxythymidine drug resistance mutations in HIV-1 reverse transcriptase can induce long range conformational changes.
  Proc Natl Acad Sci U S A, 95, 9518-9523.
PDB code: 1rt3
9772165 J.Ren, R.M.Esnouf, A.L.Hopkins, J.Warren, J.Balzarini, D.I.Stuart, and D.K.Stammers (1998).
Crystal structures of HIV-1 reverse transcriptase in complex with carboxanilide derivatives.
  Biochemistry, 37, 14394-14403.
PDB codes: 1rt4 1rt5 1rt6 1rt7
9804810 W.A.Beard, K.Bebenek, T.A.Darden, L.Li, R.Prasad, T.A.Kunkel, and S.H.Wilson (1998).
Vertical-scanning mutagenesis of a critical tryptophan in the minor groove binding track of HIV-1 reverse transcriptase. Molecular nature of polymerase-nucleic acid interactions.
  J Biol Chem, 273, 30435-30442.  
  9343170 H.Pelemans, R.Esnouf, A.Dunkler, M.A.Parniak, A.M.Vandamme, A.Karlsson, E.De Clercq, J.P.Kleim, and J.Balzarini (1997).
Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1.
  J Virol, 71, 8195-8203.  
9164459 K.Bebenek, W.A.Beard, T.A.Darden, L.Li, R.Prasad, B.A.Luton, D.G.Gorenstein, S.H.Wilson, and T.A.Kunkel (1997).
A minor groove binding track in reverse transcriptase.
  Nat Struct Biol, 4, 194-197.  
9108091 R.M.Esnouf, J.Ren, A.L.Hopkins, C.K.Ross, E.Y.Jones, D.K.Stammers, and D.I.Stuart (1997).
Unique features in the structure of the complex between HIV-1 reverse transcriptase and the bis(heteroaryl)piperazine (BHAP) U-90152 explain resistance mutations for this nonnucleoside inhibitor.
  Proc Natl Acad Sci U S A, 94, 3984-3989.
PDB code: 1klm
9384557 S.E.Zographos, N.G.Oikonomakos, K.E.Tsitsanou, D.D.Leonidas, E.D.Chrysina, V.T.Skamnaki, H.Bischoff, S.Goldmann, K.A.Watson, and L.N.Johnson (1997).
The structure of glycogen phosphorylase b with an alkyldihydropyridine-dicarboxylic acid compound, a novel and potent inhibitor.
  Structure, 5, 1413-1425.
PDB codes: 1amv 2amv
  8861970 A.M.Martín-Hernández, E.Domingo, and L.Menéndez-Arias (1996).
Human immunodeficiency virus type 1 reverse transcriptase: role of Tyr115 in deoxynucleotide binding and misinsertion fidelity of DNA synthesis.
  EMBO J, 15, 4434-4442.  
10398452 De Clercq E (1996).
What can be Expected from Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) in the Treatment of Human Immunodeficiency Virus Type 1 (HIV-1) Infections?
  Rev Med Virol, 6, 97.  
  8892891 N.Gargano, S.Biocca, A.Bradbury, and A.Cattaneo (1996).
Human recombinant antibody fragments neutralizing human immunodeficiency virus type 1 reverse transcriptase provide an experimental basis for the structural classification of the DNA polymerase family.
  J Virol, 70, 7706-7712.  
  8827210 V.R.Prasad, W.C.Drosopoulos, and M.E.Hamburgh (1996).
Perspective: research highlights at the Albert Einstein College of Medicine Center for AIDS research. Approaches to control drug resistance in HIV: the role of increased polymerase fidelity.
  AIDS Res Hum Retroviruses, 12, 959-963.  
8805568 Y.Hsiou, J.Ding, K.Das, A.D.Clark, S.H.Hughes, and E.Arnold (1996).
Structure of unliganded HIV-1 reverse transcriptase at 2.7 A resolution: implications of conformational changes for polymerization and inhibition mechanisms.
  Structure, 4, 853-860.
PDB code: 1dlo
8535785 J.Ren, R.Esnouf, A.Hopkins, C.Ross, Y.Jones, D.Stammers, and D.Stuart (1995).
The structure of HIV-1 reverse transcriptase complexed with 9-chloro-TIBO: lessons for inhibitor design.
  Structure, 3, 915-926.
PDB code: 1rev
  8535257 M.B.Kroeger Smith, C.A.Rouzer, L.A.Taneyhill, N.A.Smith, S.H.Hughes, P.L.Boyer, P.A.Janssen, H.Moereels, L.Koymans, and E.Arnold (1995).
Molecular modeling studies of HIV-1 reverse transcriptase nonnucleoside inhibitors: total energy of complexation as a predictor of drug placement and activity.
  Protein Sci, 4, 2203-2222.  
7546568 M.J.Gait, and J.Karn (1995).
Progress in anti-HIV structure-based drug design.
  Trends Biotechnol, 13, 430-438.  
8535782 M.M.Georgiadis, S.M.Jessen, C.M.Ogata, A.Telesnitsky, S.P.Goff, and W.A.Hendrickson (1995).
Mechanistic implications from the structure of a catalytic fragment of Moloney murine leukemia virus reverse transcriptase.
  Structure, 3, 879-892.
PDB code: 1mml
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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