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PDBsum entry 1rt2
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Nucleotidyltransferase PDB id
1rt2

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
543 a.a. *
402 a.a. *
Ligands
TNK
Waters ×138
* Residue conservation analysis
PDB id:
1rt2
Name: Nucleotidyltransferase
Title: Crystal structure of HIV-1 reverse transcriptase complexed with tnk- 651
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:
2.55Å     R-factor:   0.207    
Authors: J.Ren,R.Esnouf,A.Hopkins,B.Willcox,Y.Jones,C.Ross,D.Stammers,D.Stuart
Key ref: A.L.Hopkins et al. (1996). Complexes of HIV-1 reverse transcriptase with inhibitors of the HEPT series reveal conformational changes relevant to the design of potent non-nucleoside inhibitors. J Med Chem, 39, 1589-1600. PubMed id: 8648598 DOI: 10.1021/jm960056x
Date:
16-Mar-96     Release date:   21-Apr-97    
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.
402 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    
 
 
DOI no: 10.1021/jm960056x J Med Chem 39:1589-1600 (1996)
PubMed id: 8648598  
 
 
Complexes of HIV-1 reverse transcriptase with inhibitors of the HEPT series reveal conformational changes relevant to the design of potent non-nucleoside inhibitors.
A.L.Hopkins, J.Ren, R.M.Esnouf, B.E.Willcox, E.Y.Jones, C.Ross, T.Miyasaka, R.T.Walker, H.Tanaka, D.K.Stammers, D.I.Stuart.
 
  ABSTRACT  
 
Crystal structures of HIV-1 reverse transcriptase (RT) complexed with a range of chemically diverse non-nucleoside inhibitors (NNIs) have shown a single pocket in which the inhibitors bind and details of the inhibitor-protein interactions. To delineate the structural requirements for an effective inhibitor, we have determined the structures of three closely related NNIs which vary widely in their potencies. Crystal structures of HIV-1 RT complexed with two very potent inhibitors, MKC-442 and TNK-651, at 2.55 angstroms resolution complement our previous analysis of the complex with the less effective inhibitor, HEPT. These structures reveal conformational changes which correlate with changes in potency. We suggest that a major determinant of increased potency in the analogues of HEPT is an improved interaction between residue Tyr181 in the protein and the 6-benzyl ring of the inhibitors which stabilizes the structure of the complex. This arises through a conformational switching of the protein structure triggered by the steric bulk of the 5-substituent of the inhibitor pyrimidine ring.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
23314251 M.Lapkouski, L.Tian, J.T.Miller, S.F.Le Grice, and W.Yang (2013).
Complexes of HIV-1 RT, NNRTI and RNA/DNA hybrid reveal a structure compatible with RNA degradation.
  Nat Struct Mol Biol, 20, 230-236.
PDB codes: 4b3o 4b3p 4b3q
22719549 N.R.El-Brollosy, M.I.Attia, A.A.El-Emam, S.W.Ng, and E.R.Tiekink (2012).
6-Methyl-1-({[(2E)-2-methyl-3-phenyl-prop-2-en-1-yl]-oxy}meth-yl)-1,2,3,4-tetra-hydro-quinazoline-2,4-dione.
  Acta Crystallogr Sect E Struct Rep Online, 68, o1768-o1769.  
22719550 N.R.El-Brollosy, M.I.Attia, A.A.El-Emam, S.W.Ng, and E.R.Tiekink (2012).
6-Chloro-1-({[(2E)-2-methyl-3-phenyl-prop-2-en-1-yl]-oxy}meth-yl)-1,2,3,4-tetra-hydro-quinazoline-2,4-dione.
  Acta Crystallogr Sect E Struct Rep Online, 68, o1770-o1771.  
22589903 N.R.El-Brollosy, M.I.Attia, H.A.Ghabbour, S.Chantrapromma, and H.K.Fun (2012).
6-(3,5-Dimethyl-benz-yl)-5-ethyl-1-[(2-phenyl-eth-oxy)meth-yl]pyrimidine-2,4(1H,3H)dione.
  Acta Crystallogr Sect E Struct Rep Online, 68, o1031-o1032.  
22719629 N.R.El-Brollosy, N.Dege, G.Demirtaş, M.I.Attia, A.A.El-Emam, and O.Büyükgüngör (2012).
1-{[(2,3-Dihydro-1H-inden-2-yl)-oxy]meth-yl}quinazoline-2,4(1H,3H)-dione.
  Acta Crystallogr Sect E Struct Rep Online, 68, o1866-o1867.  
21275045 L.Q.Al-Mawsawi, and N.Neamati (2011).
Allosteric Inhibitor Development Targeting HIV-1 Integrase.
  ChemMedChem, 6, 228-241.  
  21322110 M.Yu, Z.Li, S.Liu, E.Fan, C.Pannecouque, E.De Clercq, and X.Liu (2011).
Synthesis and biological evaluation of 6-substituted 5-alkyl-2-(phenylaminocarbonylmethylthio)pyrimidin-4(3H)-ones as potent HIV-1 NNRTIs.
  ChemMedChem, 6, 826-833.  
20583854 P.Decha, P.Intharathep, T.Udommaneethanakit, P.Sompornpisut, S.Hannongbua, P.Wolschann, and V.Parasuk (2011).
Theoretical studies on the molecular basis of HIV-1RT/NNRTIs interactions.
  J Enzyme Inhib Med Chem, 26, 29-36.  
21134218 Z.Li, H.Zhang, Y.Li, J.Zhang, and H.F.Chen (2011).
Drug resistant mechanism of diaryltriazine analog inhibitors of HIV-1 reverse transcriptase using molecular dynamics simulation and 3D-QSAR.
  Chem Biol Drug Des, 77, 63-74.  
20535242 S.Ganguly, S.Murugesan, N.Prasanthi, O.Alptürk, B.Herman, and N.Sluis-Cremer (2010).
Synthesis and Anti-HIV-1 Activity of a Novel Series of Aminoimidazole Analogs.
  Lett Drug Des Discov, 7, 318-323.  
19289522 M.T.Lai, V.Munshi, S.Touch, R.M.Tynebor, T.J.Tucker, P.M.McKenna, T.M.Williams, D.J.DiStefano, D.J.Hazuda, and M.D.Miller (2009).
Antiviral activity of MK-4965, a novel nonnucleoside reverse transcriptase inhibitor.
  Antimicrob Agents Chemother, 53, 2424-2431.  
19856332 N.R.El-Brollosy, O.A.Al-Deeb, A.A.El-Emam, E.B.Pedersen, P.La Colla, G.Collu, G.Sanna, and R.Loddo (2009).
Synthesis of novel uracil non-nucleoside derivatives as potential reverse transcriptase inhibitors of HIV-1.
  Arch Pharm (Weinheim), 342, 663-670.  
18785154 N.S.Sapre, S.Gupta, N.Pancholi, and N.Sapre (2009).
A group center overlap based approach for "3D QSAR" studies on TIBO derivatives.
  J Comput Chem, 30, 922-933.  
19374380 S.E.Nichols, R.A.Domaoal, V.V.Thakur, J.Tirado-Rives, K.S.Anderson, and W.L.Jorgensen (2009).
Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures.
  J Chem Inf Model, 49, 1272-1279.  
17904371 K.Danel, L.M.Larsen, E.B.Pedersen, G.Sanna, P.La Colla, and R.Loddo (2008).
Synthesis and antiviral activity of new dimeric inhibitors against HIV-1.
  Bioorg Med Chem, 16, 511-517.  
18081133 M.Radi, C.Falciani, L.Contemori, E.Petricci, G.Maga, A.Samuele, S.Zanoli, M.Terrazas, M.Castria, A.Togninelli, J.A.Esté, I.Clotet-Codina, M.Armand-Ugón, and M.Botta (2008).
A multidisciplinary approach for the identification of novel HIV-1 non-nucleoside reverse transcriptase inhibitors: S-DABOCs and DAVPs.
  ChemMedChem, 3, 573-593.  
18642033 N.S.Sapre, S.Gupta, N.Pancholi, and N.Sapre (2008).
Data mining using template-based molecular docking on tetrahydroimidazo-[4,5,1-jk][1,4]-benzodiazepinone (TIBO) derivatives as HIV-1RT inhibitors.
  J Mol Model, 14, 1009-1021.  
18217215 R.D.Clark (2008).
A ligand's-eye view of protein binding.
  J Comput Aided Mol Des, 22, 507-521.  
19012571 Z.Li, J.Han, and H.F.Chen (2008).
Revealing interaction mode between HIV-1 reverse transcriptase and diaryltriazine analog inhibitor.
  Chem Biol Drug Des, 72, 350-359.  
17949071 G.Barreiro, C.R.Guimarães, I.Tubert-Brohman, T.M.Lyons, J.Tirado-Rives, and W.L.Jorgensen (2007).
Search for non-nucleoside inhibitors of HIV-1 reverse transcriptase using chemical similarity, molecular docking, and MM-GB/SA scoring.
  J Chem Inf Model, 47, 2416-2428.  
17690926 N.J.English (2007).
Calculation of binding affinities of HIV-1 RT and beta-secretase inhibitors using the linear interaction energy method with explicit and continuum solvation approaches.
  J Mol Model, 13, 1081-1097.  
17464964 Y.L.Aly, E.B.Pedersen, P.La Colla, and R.Loddo (2007).
Synthesis and anti-HIV-1 activity of new MKC-442 analogues with an alkynyl-substituted 6-benzyl group.
  Arch Pharm (Weinheim), 340, 225-235.  
16911530 J.Ren, C.E.Nichols, A.Stamp, P.P.Chamberlain, R.Ferris, K.L.Weaver, S.A.Short, and D.K.Stammers (2006).
Structural insights into mechanisms of non-nucleoside drug resistance for HIV-1 reverse transcriptases mutated at codons 101 or 138.
  FEBS J, 273, 3850-3860.
PDB codes: 2hnd 2hny 2hnz
16946529 L.Ji, F.E.Chen, X.Q.Feng, E.De Clercq, J.Balzarini, and C.Pannecouque (2006).
Non-nucleoside HIV-1 reverse transcriptase inhibitors, Part 7. Synthesis, antiviral activity, and 3D-QSAR investigations of novel 6-(1-naphthoyl) HEPT analogues.
  Chem Pharm Bull (Tokyo), 54, 1248-1253.  
16763521 R.A.Domaoal, R.A.Bambara, and L.M.Demeter (2006).
HIV-1 reverse transcriptase mutants resistant to nonnucleoside reverse transcriptase inhibitors do not adversely affect DNA synthesis: pre-steady-state and steady-state kinetic studies.
  J Acquir Immune Defic Syndr, 42, 405-411.  
16508186 T.Maruyama, S.Kozai, Y.Demizu, M.Witvrouw, C.Pannecouque, J.Balzarini, R.Snoecks, G.Andrei, and E.De Clercq (2006).
Synthesis and anti-HIV-1 and anti-HCMV activity of 1-substituted 3-(3,5-dimethylbenzyl)uracil derivatives.
  Chem Pharm Bull (Tokyo), 54, 325-333.  
17036113 X.Wang, Q.Lou, Y.Guo, Y.Xu, Z.Zhang, and J.Liu (2006).
The design and synthesis of 9-phenylcyclohepta[d]pyrimidine-2,4-dione derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase.
  Org Biomol Chem, 4, 3252-3258.  
15996003 E.R.Sørensen, N.R.El-Brollosy, P.T.Jørgensen, E.B.Pedersen, and C.Nielsen (2005).
Synthesis of 6-(3,5-dichlorobenzyl) derivatives as isosteric analogues of the HIV drug 6-(3,5-dimethylbenzyl)-1-(ethoxymethyl)-5-isopropyluracil (GCA-186).
  Arch Pharm (Weinheim), 338, 299-304.  
16079514 G.F.Sun, X.X.Chen, F.E.Chen, Y.P.Wang, E.De Clercq, J.Balzarini, and C.Pannecouque (2005).
Nonnucleoside HIV-1 reverse-transcriptase inhibitors, part 5. Synthesis and anti-HIV-1 activity of novel 6-naphthylthio HEPT analogues.
  Chem Pharm Bull (Tokyo), 53, 886-892.  
16211654 G.F.Sun, Y.Y.Kuang, F.E.Chen, E.De Clercq, J.Balzarini, and C.Pannecouque (2005).
Non-nucleoside HIV reverse transcriptase inhibitors, Part 6[1]: synthesis and anti-HIV activity of novel 2-[(arylcarbonylmethyl)thio]-6-arylthio DABO analogues.
  Arch Pharm (Weinheim), 338, 457-461.  
16163451 H.F.Chen, B.T.Fan, C.Y.Zhao, L.Xie, C.H.Zhao, T.Zhou, K.H.Lee, and G.Allaway (2005).
Computational studies and drug design for HIV-1 reverse transcriptase inhibitors of 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs.
  J Comput Aided Mol Des, 19, 243-258.  
16163450 J.L.Medina-Franco, A.Golbraikh, S.Oloff, R.Castillo, and A.Tropsha (2005).
Quantitative structure-activity relationship analysis of pyridinone HIV-1 reverse transcriptase inhibitors using the k nearest neighbor method and QSAR-based database mining.
  J Comput Aided Mol Des, 19, 229-242.  
15629197 J.Ren, and D.K.Stammers (2005).
HIV reverse transcriptase structures: designing new inhibitors and understanding mechanisms of drug resistance.
  Trends Pharmacol Sci, 26, 4-7.  
15016861 E.N.Peletskaya, A.A.Kogon, S.Tuske, E.Arnold, and S.H.Hughes (2004).
Nonnucleoside inhibitor binding affects the interactions of the fingers subdomain of human immunodeficiency virus type 1 reverse transcriptase with DNA.
  J Virol, 78, 3387-3397.
PDB code: 1r0a
14748000 F.Daeyaert, M.de Jonge, J.Heeres, L.Koymans, P.Lewi, M.H.Vinkers, and P.A.Janssen (2004).
A pharmacophore docking algorithm and its application to the cross-docking of 18 HIV-NNRTI's in their binding pockets.
  Proteins, 54, 526-533.  
15249669 J.D.Pata, W.G.Stirtan, S.W.Goldstein, and T.A.Steitz (2004).
Structure of HIV-1 reverse transcriptase bound to an inhibitor active against mutant reverse transcriptases resistant to other nonnucleoside inhibitors.
  Proc Natl Acad Sci U S A, 101, 10548-10553.
PDB code: 1tv6
15229890 M.Barbany, H.Gutiérrez-de-Terán, F.Sanz, and J.Villà-Freixa (2004).
Towards a MIP-based alignment and docking in computer-aided drug design.
  Proteins, 56, 585-594.  
15544453 N.Sluis-Cremer, N.A.Temiz, and I.Bahar (2004).
Conformational changes in HIV-1 reverse transcriptase induced by nonnucleoside reverse transcriptase inhibitor binding.
  Curr HIV Res, 2, 323-332.  
12843582 G.Meng, F.E.Chen, E.De Clercq, J.Balzarini, and C.Pannecouque (2003).
Nonnucleoside HIV-1 reverse transcriptase inhibitors: Part I. Synthesis and structure-activity relationship of 1-alkoxymethyl-5-alkyl-6-naphthylmethyl uracils as HEPT analogues.
  Chem Pharm Bull (Tokyo), 51, 779-789.  
12651859 J.L.Jeffrey, J.Y.Feng, C.C.Qi, K.S.Anderson, and P.A.Furman (2003).
Dioxolane guanosine 5'-triphosphate, an alternative substrate inhibitor of wild-type and mutant HIV-1 reverse transcriptase. Steady state and pre-steady state kinetic analyses.
  J Biol Chem, 278, 18971-18979.  
12838268 S.J.Teague (2003).
Implications of protein flexibility for drug discovery.
  Nat Rev Drug Discov, 2, 527-541.  
12808237 T.Miyashita, M.Baba, S.Shigeta, K.Mori, and K.Shinozuka (2003).
Synthesis and anti-HIV-1 activity of novel 10-thiaisoalloxazines, a structural analog of C-5 and/or C-6 substituted pyrimidine acyclonucleoside.
  Chem Pharm Bull (Tokyo), 51, 630-634.  
11939780 J.W.Rausch, D.Lener, J.T.Miller, J.G.Julias, S.H.Hughes, and S.F.Le Grice (2002).
Altering the RNase H primer grip of human immunodeficiency virus reverse transcriptase modifies cleavage specificity.
  Biochemistry, 41, 4856-4865.  
12050397 P.R.Harrigan, M.Salim, D.K.Stammers, B.Wynhoven, Z.L.Brumme, P.McKenna, B.Larder, and S.D.Kemp (2002).
A mutation in the 3' region of the human immunodeficiency virus type 1 reverse transcriptase (Y318F) associated with nonnucleoside reverse transcriptase inhibitor resistance.
  J Virol, 76, 6836-6840.  
11533206 E.N.Peletskaya, P.L.Boyer, A.A.Kogon, P.Clark, H.Kroth, J.M.Sayer, D.M.Jerina, and S.H.Hughes (2001).
Cross-linking of the fingers subdomain of human immunodeficiency virus type 1 reverse transcriptase to template-primer.
  J Virol, 75, 9435-9445.  
11170249 M.Quaglia, A.Mai, G.Sbardella, M.Artico, R.Ragno, S.Massa, D.del Piano, G.Setzu, S.Doratiotto, and V.Cotichini (2001).
Chiral resolution and molecular modeling investigation of rac-2-cyclopentylthio-6-[1-(2,6-difluorophenyl)ethyl]-3,4-dihydro-5-methylpyrimidin-4(3H)-one (MC-1047), a potent anti-HIV-1 reverse transcriptase agent of the DABO class.
  Chirality, 13, 75-80.  
10602732 G.M.Szczech, P.Furman, G.R.Painter, D.W.Barry, K.Borroto-Esoda, T.B.Grizzle, M.R.Blum, J.Sommadossi, R.Endoh, T.Niwa, M.Yamamoto, and C.Moxham (2000).
Safety assessment, in vitro and in vivo, and pharmacokinetics of emivirine, a potent and selective nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1.
  Antimicrob Agents Chemother, 44, 123-130.  
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
10875608 K.Van Laethem, J.C.Schmit, H.Pelemans, J.Balzarini, M.Witvrouw, M.J.Pérez-Pérez, M.J.Camarasa, R.M.Esnouf, S.Aquaro, A.Cenci, C.F.Perno, P.Hermans, S.Sprecher, L.Ruiz, B.Clotet, E.Van Wijngaerden, M.Van Ranst, J.Desmyter, E.De Clercq, and A.M.Vandamme (2000).
Presence of 2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxath iole-2",2"-dioxide) (TSAO)-resistant virus strains in TSAO-inexperienced HIV patients.
  AIDS Res Hum Retroviruses, 16, 825-833.  
10195434 L.Lawtrakul, S.Hannongbua, A.Beyer, and P.Wolschann (1999).
Conformational study of the HIV-1 reverse transcriptase inhibitor 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT).
  Biol Chem, 380, 265-267.  
9811899 D.V.Nissley, P.L.Boyer, D.J.Garfinkel, S.H.Hughes, and J.N.Strathern (1998).
Hybrid Ty1/HIV-1 elements used to detect inhibitors and monitor the activity of HIV-1 reverse transcriptase.
  Proc Natl Acad Sci U S A, 95, 13905-13910.  
  9835518 E.A.Sudbeck, C.Mao, R.Vig, T.K.Venkatachalam, L.Tuel-Ahlgren, and F.M.Uckun (1998).
Structure-based design of novel dihydroalkoxybenzyloxopyrimidine derivatives as potent nonnucleoside inhibitors of the human immunodeficiency virus reverse transcriptase.
  Antimicrob Agents Chemother, 42, 3225-3233.  
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.  
  9491916 J.Balzarini, H.Pelemans, R.Esnouf, and E.De Clercq (1998).
A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781.
  AIDS Res Hum Retroviruses, 14, 255-260.  
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
  9517942 M.Witvrouw, M.E.Arranz, C.Pannecouque, R.Declercq, H.Jonckheere, J.C.Schmit, A.M.Vandamme, J.A.Diaz, S.T.Ingate, J.Desmyter, R.Esnouf, L.Van Meervelt, S.Vega, J.Balzarini, and E.De Clercq (1998).
1,1,3-Trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazine (TTD) derivatives: a new class of nonnucleoside human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitors with anti-HIV-1 activity.
  Antimicrob Agents Chemother, 42, 618-623.  
  9624472 T.Fujiwara, A.Sato, M.el-Farrash, S.Miki, K.Abe, Y.Isaka, M.Kodama, Y.Wu, L.B.Chen, H.Harada, H.Sugimoto, M.Hatanaka, and Y.Hinuma (1998).
S-1153 inhibits replication of known drug-resistant strains of human immunodeficiency virus type 1.
  Antimicrob Agents Chemother, 42, 1340-1345.  
  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.  
9354757 J.Ding, S.H.Hughes, and E.Arnold (1997).
Protein-nucleic acid interactions and DNA conformation in a complex of human immunodeficiency virus type 1 reverse transcriptase with a double-stranded DNA template-primer.
  Biopolymers, 44, 125-138.  
9127858 P.P.Mager (1997).
A check on rational drug design: molecular simulation of the allosteric inhibition of HIV-1 reverse transcriptase.
  Med Res Rev, 17, 235-276.  
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
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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