The following are recent publications related to HIV-1 RT structure and function
from the Hughes and Arnold laboratories:
| 1:
| Morningstar
ML, Roth T, Farnsworth D, Kroeger Smith M, Watson K, Buckheit RW Jr,
Das K,
Zhang W, Arnold E, Hughes SH, Michejda CJ. | |
Synthesis,
biological activity, and crystal structure of potent non-nucleoside
inhibitors
of HIV-1 reverse transcriptase that retain activity against mutant forms
of
the enzyme.
J
Med Chem. 2007, in press.
| 2:
| Das
K, Clark AD, Lewi P, Hughes SH, Arnold E. | |
Detection
of non-nucleoside inhibitor binding to HIV-1 reverse transcriptase by dynamic
light
scattering.
Biophys
J. 2007, in press.
In
vitro analysis of the effects of mutations in the G-tract of the human immunodeficiency
virus type 1 polypurine tract on RNase H cleavage specificity.
Virology. 2006 360:341-9. Epub 2006 Nov 20.
PMID: 17123564
[PubMed - indexed for MEDLINE]
Analysis
of amino acids in the beta7-beta8 loop of human immunodeficiency virus type 1
reverse
transcriptase for their role in virus replication.
J Mol Biol. 2007 Feb 2;365(5):1368-78. Epub 2006 Nov 10.
PMID: 17141805 [PubMed - indexed for MEDLINE]
Crystal
structures of clinically relevant Lys103Asn/Tyr181Cys double mutant HIV-1
reverse
transcriptase in complexes with ATP and non-nucleoside inhibitor HBY 097.
J Mol Biol. 2007 Jan 5;365(1):77-89. Epub 2006 Sep 15.
PMID: 17056061 [PubMed - indexed for MEDLINE]
| 6:
| Himmel
DM, Sarafianos SG, Dharmasena S, Hossain MM, McCoy-Simandle K, Ilina T, Clark
AD Jr, Knight JL, Julias JG, Clark PK, Krogh-Jespersen K, Levy RM, Hughes SH,
Parniak MA, Arnold E. | Related
Articles |
HIV-1
reverse transcriptase structure with RNase H inhibitor dihydroxy benzoyl
naphthyl
hydrazone bound at a novel site.
ACS Chem Biol. 2006 Dec 20;1(11):702-12.
PMID: 17184135
[PubMed - indexed for MEDLINE]
The
history of N-methanocarbathymidine: the investigation of a conformational concept
leads
to the discovery of a potent and selective nucleoside antiviral agent.
Antiviral Res. 2006 Sep;71(2-3):268-75. Epub 2006 May 6. Review.
PMID: 16730077 [PubMed - indexed for MEDLINE]
Why
do HIV-1 and HIV-2 use different pathways to develop AZT resistance?
PLoS Pathog. 2006 Feb;2(2):e10. Epub 2006 Feb 17.
PMID:
16485036 [PubMed - indexed for MEDLINE]
Combining
mutations in HIV-1 reverse transcriptase with mutations in the HIV-1
polypurine
tract affects RNase H cleavages involved in PPT utilization.
Virology. 2006 May 10;348(2):378-88. Epub 2006 Feb 10.
PMID: 16473384 [PubMed - indexed for MEDLINE]
| 10:
| Himmel
DM, Das K, Clark AD Jr, Hughes SH, Benjahad A, Oumouch S, Guillemont J, Coupa
S, Poncelet A, Csoka I, Meyer C, Andries K, Nguyen CH, Grierson DS, Arnold E. | Related
Articles |
Crystal
structures for HIV-1 reverse transcriptase in complexes with three pyridinone
derivatives: a new class of non-nucleoside inhibitors effective against a
broad range of
drug-resistant strains.
J Med Chem. 2005 Dec 1;48(24):7582-91.
PMID: 16302798
[PubMed - indexed for MEDLINE]
| 11:
| Janssen
PA, Lewi PJ, Arnold E, Daeyaert F, de Jonge M, Heeres J, Koymans L, Vinkers M,
Guillemont J, Pasquier E, Kukla M, Ludovici D, Andries K, de Bethune MP, Pauwels
R, Das K, Clark AD Jr, Frenkel YV, Hughes SH, Medaer B, De Knaep F, Bohets H,
De Clerck F, Lampo A, Williams P, Stoffels P. | Related
Articles |
In
search of a novel anti-HIV drug: multidisciplinary coordination in the discovery
of
4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2- pyrimidinyl]amino]
benzonitrile
(R278474, rilpivirine).
J Med Chem. 2005 Mar 24;48(6):1901-9. Review.
PMID: 15771434
[PubMed - indexed for MEDLINE]
Crystallography
and the design of anti-AIDS drugs: conformational flexibility and
positional
adaptability are important in the design of non-nucleoside HIV-1 reverse
transcriptase
inhibitors.
Prog
Biophys Mol Biol. 2005 Jun;88(2):209-31. Review.
PMID: 15572156 [PubMed -
indexed for MEDLINE]
Fixed
conformation nucleoside analogs effectively inhibit excision-proficient HIV-1
reverse
transcriptases.
J
Mol Biol. 2005 Jan 21;345(3):441-50.
PMID: 15581889 [PubMed - indexed for
MEDLINE]
Taking
aim at a moving target: designing drugs to inhibit drug-resistant HIV-1 reverse
transcriptases.
Curr
Opin Struct Biol. 2004 Dec;14(6):716-30. Review.
PMID: 15582396 [PubMed -
indexed for MEDLINE]
In
vitro characterization of a simian immunodeficiency virus-human immunodeficiency
virus (HIV) chimera expressing HIV type 1 reverse transcriptase to study antiviral
resistance
in pigtail macaques.
J
Virol. 2004 Dec;78(24):13553-61.
PMID: 15564466 [PubMed - indexed for MEDLINE]
Effects
of mutations in the G tract of the human immunodeficiency virus type 1
polypurine
tract on virus replication and RNase H cleavage.
J Virol. 2004 Dec;78(23):13315-24.
PMID: 15542682 [PubMed
- indexed for MEDLINE]
Effects
of the Delta67 complex of mutations in human immunodeficiency
virus type 1
reverse transcriptase on nucleoside analog excision.
J Virol. 2004 Sep;78(18):9987-97.
PMID: 15331732 [PubMed
- indexed for MEDLINE]
Designing
anti-AIDS drugs targeting the major mechanism of HIV-1 RT
resistance to nucleoside
analog drugs.
Int
J Biochem Cell Biol. 2004 Sep;36(9):1706-15.
PMID: 15183339 [PubMed - indexed
for MEDLINE]
Characterization
of the polymerase and RNase H activities of human foamy
virus reverse transcriptase.
J Virol. 2004 Jun;78(12):6112-21.
PMID: 15163704 [PubMed
- indexed for MEDLINE]
| 20:
| 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. | Related
Articles |
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.
PMID: 15107837 [PubMed
- indexed for MEDLINE]
| 21:
| Das
K, Clark AD Jr, Lewi PJ, Heeres J, De Jonge MR, Koymans LM,
Vinkers HM, Daeyaert
F, Ludovici DW, Kukla MJ, De Corte B, Kavash RW,
Ho CY, Ye H, Lichtenstein
MA, Andries K, Pauwels R, De Bethune MP,
Boyer PL, Clark P, Hughes SH, Janssen
PA, Arnold E. | Related
Articles |
Roles
of conformational and positional adaptability in structure-based design
of
TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase
inhibitors
that are highly potent and effective against wild-type and drug-
resistant
HIV-1 variants.
J
Med Chem. 2004 May 6;47(10):2550-60.
PMID: 15115397 [PubMed - indexed for MEDLINE]
Mutations
at position 184 of human immunodeficiency virus type-1 reverse
transcriptase
affect virus titer and viral DNA synthesis.
Virology. 2004 Apr 25;322(1):13-21.
PMID: 15063112 [PubMed
- indexed for MEDLINE]
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.
PMID: 15016861 [PubMed
- indexed for MEDLINE]
PCR
amplification of DNA containing non-standard base pairs by variants of
reverse
transcriptase from Human Immunodeficiency Virus-1.
Nucleic Acids Res. 2004 Feb 02;32(2):728-35. Print 2004.
PMID:
14757837 [PubMed - indexed for MEDLINE]
Mutations
in the 5' end of the human immunodeficiency virus type 1
polypurine tract affect
RNase H cleavage specificity and virus titer.
J Virol. 2003 Oct;77(20):11150-7.
PMID: 14512562 [PubMed
- indexed for MEDLINE]
| 26:
| Lewis
PJ, de Jonge M, Daeyaert F, Koymans L, Vinkers M, Heeres J,
Janssen PA, Arnold
E, Das K, Clark AD Jr, Hughes SH, Boyer PL,
de Bethune MP, Pauwels R, Andries
K, Kukla M, Ludovici D, De Corte B,
Kavash R, Ho C. | Related
Articles |
On
the detection of multiple-binding modes of ligands to proteins, from
biological,
structural, and modeling data.
J Comput Aided Mol Des. 2003 Feb-Apr;17(2-4):129-34.
PMID:
13677481 [PubMed - indexed for MEDLINE]
Mutation
of amino acids in the connection domain of human immunodeficiency
virus type
1 reverse transcriptase that contact the template-primer affects
RNase H activity.
J Virol. 2003 Aug;77(15):8548-54.
PMID: 12857924 [PubMed
- indexed for MEDLINE]
| 28:
| Choi
Y, George C, Comin MJ, Barchi JJ Jr, Kim HS, Jacobson KA,
Balzarini J, Mitsuya
H, Boyer PL, Hughes SH, Marquez VE. | Related
Articles |
A
conformationally locked analogue of the anti-HIV agent stavudine. An important
correlation
between pseudorotation and maximum amplitude.
J Med Chem. 2003 Jul 17;46(15):3292-9.
PMID: 12852759 [PubMed
- indexed for MEDLINE]
| 29:
| Kroeger
Smith MB, Hose BM, Hawkins A, Lipchock J, Farnsworth DW,
Rizzo RC, Tirado-Rives
J, Arnold E, Zhang W, Hughes SH, Jorgensen WL,
Michejda CJ, Smith RH Jr. | Related
Articles |
Molecular
modeling calculations of HIV-1 reverse transcriptase nonnucleoside
inhibitors:
correlation of binding energy with biological activity for novel 2-aryl-
substituted
benzimidazole analogues.
J Med Chem. 2003 May 8;46(10):1940-7.
PMID: 12723956 [PubMed
- indexed for MEDLINE]
| 30:
| Sarafianos
SG, Clark AD Jr, Tuske S, Squire CJ, Das K, Sheng D, Ilankumaran P, Ramesha AR,
Kroth H, Sayer JM, Jerina DM, Boyer PL, Hughes SH, Arnold E. | Related
Articles |
Trapping
HIV-1 reverse transcriptase before and after translocation on DNA.
J Biol Chem. 2003 Jan 28 [epub ahead of print]
PMID: 12554739
[PubMed - as supplied by publisher]
| 31:
| Skillman
AG, Maurer KW, Roe DC, Stauber MJ, Eargle D, Ewing TJ, Muscate A, Davioud-Charvet
E, Medaglia MV, Fisher RJ, Arnold E, Gao HQ, Buckheit R,
Boyer PL, Hughes
SH, Kuntz ID, Kenyon GL. | Related
Articles |
A
novel mechanism for inhibition of HIV-1 reverse transcriptase.
Bioorg Chem. 2002 Dec;30(6):443-58.
PMID: 12642128 [PubMed
- in process]
Nucleoside
analog resistance caused by insertions in the fingers of human
immunodeficiency
virus type 1 reverse transcriptase involves ATP-mediated excision.
J Virol. 2002 Sep;76(18):9143-51.
PMID: 12186898 [PubMed
- indexed for MEDLINE]
| 33:
| 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. | Related
Articles |
Structures
of HIV-1 reverse transcriptase with pre- and post-translocation AZTMP-
terminated
DNA.
EMBO
J. 2002 Dec 2;21(23):6614-24.
PMID: 12456667 [PubMed - indexed for MEDLINE]
Mutations
in the RNase H domain of HIV-1 reverse transcriptase affect the initiation
of DNA synthesis and the specificity of RNase H cleavage in vivo.
Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9515-20.
PMID:
12093908 [PubMed - indexed for MEDLINE]
Mutation
of the catalytic domain of the foamy virus reverse transcriptase leads to
loss of processivity and infectivity.
J Virol. 2002 Aug;76(15):7560-70.
PMID: 12097569 [PubMed
- indexed for MEDLINE]
Nontemplated
nucleotide addition by HIV-1 reverse transcriptase.
Biochemistry. 2002 May 7;41(18):5894-906.
PMID: 11980493
[PubMed - indexed for MEDLINE]
Altering
the RNase H primer grip of human immunodeficiency virus reverse
transcriptase
modifies cleavage specificity.
Biochemistry. 2002 Apr 16;41(15):4856-65.
PMID: 11939780
[PubMed - indexed for MEDLINE]
Nontemplated
base addition by HIV-1 RT can induce nonspecific strand transfer
in vitro.
Virology. 2002 Mar 1;294(1):122-34.
PMID: 11886271 [PubMed
- indexed for MEDLINE]
The
M184V mutation reduces the selective excision of zidovudine 5'-monophosphate
(AZTMP) by the reverse transcriptase of human immunodeficiency virus type 1.
J Virol. 2002 Apr;76(7):3248-56.
PMID: 11884549 [PubMed
- indexed for MEDLINE]
RNase
H cleavage of the 5' end of the human immunodeficiency virus type 1 genome.
J Virol. 2001 Dec;75(23):11874-80.
PMID: 11689669 [PubMed
- indexed for MEDLINE]
The
ribonuclease H activity of the reverse transcriptases of human immunodeficiency
viruses type 1 and type 2 is affected by the thumb subdomain of the small protein
subunits.
J
Mol Biol. 2001 Aug 31;311(5):957-71.
PMID: 11531332 [PubMed - indexed for MEDLINE]
Cross-linking
of the fingers subdomain of human immunodeficiency virus type 1
reverse transcriptase
to template-primer.
J
Virol. 2001 Oct;75(19):9435-45.
PMID: 11533206 [PubMed - indexed for MEDLINE]
Molecular
matchmaking: NNRTIs can enhance the dimerization of HIV type 1
reverse transcriptase.
Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):6991-2. No abstract
available.
PMID: 11416176 [PubMed - indexed for MEDLINE]
Replication
of phenotypically mixed human immunodeficiency virus type 1 virions
containing
catalytically active and catalytically inactive reverse transcriptase.
J Virol. 2001 Jul;75(14):6537-46.
PMID: 11413321 [PubMed
- indexed for MEDLINE]
YADD
mutants of human immunodeficiency virus type 1 and Moloney murine
leukemia
virus reverse transcriptase are resistant to lamivudine triphosphate
(3TCTP)
in vitro.
J
Virol. 2001 Jul;75(14):6321-8.
PMID: 11413298 [PubMed - indexed for MEDLINE]
| 46:
| Hsiou
Y, Ding J, Das K, Clark AD Jr, Boyer PL, Lewi P, Janssen PA, Kleim JP,
Rosner
M, Hughes SH, Arnold E. | Related
Articles |
The
Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance.
J Mol Biol. 2001 Jun 1;309(2):437-45.
PMID: 11371163 [PubMed
- indexed for MEDLINE]
Self-priming
of retroviral minus-strand strong-stop DNAs.
Virology. 2001 Jul 5;285(2):278-90.
PMID: 11437662 [PubMed
- indexed for MEDLINE]
Adaptation
of chimeric retroviruses in vitro and in vivo: isolation of avian
retroviral
vectors with extended host range.
J Virol. 2001 Jun;75(11):4973-83.
PMID: 11333876 [PubMed
- indexed for MEDLINE]
Selective
excision of AZTMP by drug-resistant human immunodeficiency virus
reverse transcriptase.
J Virol. 2001 May;75(10):4832-42.
PMID: 11312355 [PubMed
- indexed for MEDLINE]
The
basic loop of the RNase H domain of MLV RT is important both for RNase H
and
for polymerase activity.
Virology. 2001 Mar 30;282(1):206-13.
PMID: 11259203 [PubMed
- indexed for MEDLINE]
Crystal
structure of HIV-1 reverse transcriptase in complex with a polypurine
tract
RNA:DNA.
EMBO
J. 2001 Mar 15;20(6):1449-61.
PMID: 11250910 [PubMed - indexed for MEDLINE]
In
vitro analysis of human immunodeficiency virus type 1 minus-strand strong-stop
DNA synthesis and genomic RNA processing.
J Virol. 2001 Jan;75(2):672-86.
PMID: 11134281 [PubMed
- indexed for MEDLINE]
Human
immunodeficiency virus type 1 nucleocapsid protein can prevent
self-priming
of minus-strand strong stop DNA by promoting the annealing of
short oligonucleotides
to hairpin sequences.
J
Virol. 2000 Oct;74(19):8785-92.
PMID: 10982320 [PubMed - indexed for MEDLINE]
Effects
of amino acid substitutions at position 115 on the fidelity of human
immunodeficiency
virus type 1 reverse transcriptase.
J Virol. 2000 Jul;74(14):6494-500.
PMID: 10864662 [PubMed
- indexed for MEDLINE]
The
role of steric hindrance in 3TC resistance of human immunodeficiency virus
type-1 reverse transcriptase.
J Mol Biol. 2000 Jul 7;300(2):403-18.
PMID: 10873473 [PubMed
- indexed for MEDLINE]
Analysis
of mutations at positions 115 and 116 in the dNTP binding site of HIV-1
reverse
transcriptase.
Proc
Natl Acad Sci U S A. 2000 Mar 28;97(7):3056-61.
PMID: 10737786 [PubMed - indexed
for MEDLINE]
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