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Our Science – Le Grice Website

Stuart F.J. Le Grice, Ph.D.

Selected Publications

1)  Rausch J, Chelico L, Goodman M, Le Grice S.
Dissecting APOBEC3G substrate specificity by nucleoside analog interference.
J Biol Chem. 2009.
Full Text Article. In Press. [Journal]
2)  Wilkinson TA, Januszyk K, Phillips ML, Tekeste SS, Zhang M, Miller JT, Le Grice SF, Clubb RT, Chow SA.
Identifying and characterizing a functional HIV-1 reverse transcriptase-binding site on integrase.
J. Biol. Chem. 2009.
[Journal]
3)  Wendeler M, Beilhartz G, Beutler J, Götte M, Le Grice S.
HIV ribonuclease H: Continuing the search for small molecule antagonists.
HIV Ther. 3: 39-53, 2009.
Full Text Article. [Journal]
4)  Wendeler M, Le Grice S.
HIV-1 reverse transcriptase. In: Viral Genome Replication (M Gotte, CE Cameron, and K Raney, eds). Volume .
New York: Springer Publications Company; 2009. In Press. [Book Chapter]
5)  Liu S, Abbondanzieri EA, Rausch JW, Le Grice SF, Zhuang X.
Slide into action: dynamic shuttling of HIV reverse transcriptase on nucleic acid substrates.
Science. 322: 1092-7, 2008.
[Journal]
6)  Dash C, Scarth BJ, Badorrek C, Götte M, Le Grice SF.
Examining the ribonuclease H primer grip of HIV-1 reverse transcriptase by charge neutralization of RNA/DNA hybrids.
Nucleic Acids Res. 36: 6363-71, 2008.
[Journal]
7)  Ehteshami M, Scarth BJ, Tchesnokov EP, Dash C, Le Grice SF, Hallenberger S, Jochmans D, Götte M.
Mutations M184V and Y115F in HIV-1 reverse transcriptase discriminate against nucleotide-competing reverse transcriptase inhibitors.
J. Biol. Chem. 2008.
[Journal]
8)  Wendeler M, Lee HF, Bermingham A, Miller JT, Chertov O, Bona MK, Baichoo NS, Ehteshami M, Beutler J, O'Keefe BR, Götte M, Kvaratskhelia M, Le Grice S.
Vinylogous ureas as a novel class of inhibitors of reverse transcriptase-associated ribonuclease H activity.
ACS Chem. Biol. 3: 635-44, 2008.
[Journal]
9)  Bokesch HR, Wamiru A, Le Grice SF, Beutler JA, McKee TC, McMahon JB.
HIV-1 ribonuclease H inhibitory phenolic glycosides from Eugenia hyemalis.
J. Nat. Prod. 71: 1634-6, 2008.
[Journal]
10)  Legiewicz M, Badorrek CS, Turner KB, Fabris D, Hamm TE, Rekosh D, Hammarskjöld ML, Le Grice SF.
Resistance to RevM10 inhibition reflects a conformational switch in the HIV-1 Rev response element.
Proc. Natl. Acad. Sci. U.S.A. 105: 14365-70, 2008.
[Journal]
11)  Kvaratskhelia M, LeGrice S.
Structural analysis of protein-RNA interactions with mass spectrometry.
Methods Mol Biol. 488: 213-220, 2008.
[Journal]
12)  Abbondanzieri EA, Bokinsky G, Rausch JW, Zhang JX, Le Grice SF, Zhuang X.
Dynamic binding orientations direct activity of HIV reverse transcriptase.
Nature. 453: 184-9, 2008.
[Journal]
13)  Marchand C, Beutler JA, Wamiru A, Budihas S, Mollmann U, Heinisch L, Mellors JW, Le Grice SF, Pommier Y.
Madurahydroxylactone Derivatives as Dual Inhibitors of Human Immunodeficiency Virus Type 1 Integrase and RNase H.
Antimicrob. Agents Chemother. 52: 361-4, 2008.
[Journal]
14)  Efroni S, Duttagupta R, Cheng J, Dehghani H, Hoeppner DJ, Dash C, Bazett-Jones DP, Le Grice S, McKay RD, Buetow KH, Gingeras TR, Misteli T, Meshorer E.
Global transcription in pluripotent embryonic stem cells.
Cell stem cell. 2: 437-47, 2008.
[Journal]
15)  Yi-Brunozzi HY, Brinson RG, Brabazon DM, Lener D, Le Grice SF, Marino JP.
High-Resolution NMR Analysis of the Conformations of Native and Base Analog Substituted Retroviral and LTR-Retrotransposon PPT Primers.
Chem. Biol. 15: 254-62, 2008.
[Journal]
16)  Turner KB, Brinson RG, Yi-Brunozzi HY, Rausch JW, Miller JT, Le Grice SF, Marino JP, Fabris D.
Structural probing of the HIV-1 polypurine tract RNA:DNA hybrid using classic nucleic acid ligands.
Nucleic Acids Res. 36: 2799-810, 2008.
[Journal]
17)  Klarmann GJ, Eisenhauer BM, Zhang Y, Gotte M, Pata JD, Chatterjee DK, Hecht SM, Le Grice SF.
Investigating the 'steric gate' of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase by targeted insertion of unnatural amino acids.
Biochemistry. 46: 2118-26, 2007.
Full Text Article. [Journal]
18)  Dat NT, Bae K, Wamiru A, McMahon JB, Le Grice SF, Bona M, Beutler JA, Kim YH.
A dimeric lactone from Ardisia japonica with inhibitory activity for HIV-1 and HIV-2 ribonuclease H.
J. Nat. Prod. 70: 839-41, 2007.
[Journal]
19)  Rausch JW, Le Grice SF.
Purine analog substitution of the HIV-1 polypurine tract primer defines regions controlling initiation of plus-strand DNA synthesis.
Nucleic Acids Res. 35: 256-68, 2007.
[Journal]
20)  Rausch JW, Le Grice SF.
Exploiting structurally diverse nucleoside analogs as probes of reverse transcription complexes.
Curr. HIV Res. 5: 11-22, 2007.
[Journal]
21)  Takada K, Bermingham A, O'Keefe BR, Wamiru A, Beutler JA, Le Grice SF, Lloyd J, Gustafson KR, McMahon JB.
An HIV RNase H inhibitory 1,3,4,5-tetragalloylapiitol from the African plant Hylodendron gabunensis.
J. Nat. Prod. 70: 1647-9, 2007.
[Journal]
22)  El Omari K, Ren J, Bird LE, Bona MK, Klarmann G, LeGrice SF, Stammers DK.
Molecular architecture and ligand recognition determinants for T4 RNA ligase.
J Biol Chem. 281: 1573-9, 2006.
[Journal]
23)  Dash C, Fisher TS, Prasad VR, Le Grice SF.
Examining interactions of HIV-1 reverse transcriptase with single-stranded template nucleotides by nucleoside analog interference.
J. Biol. Chem. 281: 27873-81, 2006.
[Journal]
24)  Mandal D, Dash C, Le Grice SF, Prasad VR.
Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function.
Nucleic Acids Res. 34: 2853-63, 2006.
[Journal]
25)  Dash C, Marino JP, Le Grice SF.
Examining ty3 polypurine tract structure and function by nucleoside analog interference.
J Biol Chem. 281: 2773-83, 2006.
[Journal]
26)  Bampi C, Bibillo A, Wendeler M, Divita G, Gorelick RJ, Le Grice SF, Darlix JL.
Nucleotide excision repair and template-independent addition by HIV-1 reverse transcriptase in the presence of nucleocapsid protein.
J Biol Chem. 281: 11736-11743, 2006.
[Journal]
27)  Yi-Brunozzi HY, Le Grice SF.
Investigating HIV-1 polypurine tract geometry via targeted insertion of abasic lesions in the (-)-DNA template and (+)-RNA primer.
J Biol Chem. 280: 20154-62, 2005.
[Journal]
28)  Bibillo A, Lener D, Klarmann GJ, Le Grice SF.
Functional roles of carboxylate residues comprising the DNA polymerase active site triad of Ty3 reverse transcriptase.
Nucleic Acids Res. 33: 171-81, 2005.
[Journal]
29)  Williams KL, Zhang Y, Shkriabai N, Karki RG, Nicklaus MC, Kotrikadze N, Hess S, Le Grice SF, Craigie R, Pathak VK, Kvaratskhelia M.
Mass spectrometric analysis of the HIV-1 integrase-pyridoxal 5'-phosphate complex reveals a new binding site for a nucleotide inhibitor.
J Biol Chem. 280: 7949-55, 2005.
[Journal]
30)  Ignatov ME, Berdis AJ, Le Grice SF, Barkley MD.
Attenuation of DNA replication by HIV-1 reverse transcriptase near the central termination sequence.
Biochemistry. 44: 5346-56, 2005.
[Journal]
31)  Yi-Brunozzi HY, Brabazon DM, Lener D, Le Grice SF, Marino JP.
A Ribose Sugar Conformational Switch in the LTR-Retrotransposon Ty3 Polypurine Tract-Containing RNA/DNA Hybrid.
J Am Chem Soc. 127: 16344-16345, 2005.
[Journal]
32)  Budihas SR, Gorshkova I, Gaidamakov S, Wamiru A, Bona MK, Parniak MA, Crouch RJ, McMahon JB, Beutler JA, Le Grice SF.
Selective inhibition of HIV-1 reverse transcriptase-associated ribonuclease H activity by hydroxylated tropolones.
Nucleic Acids Res. 33: 1249-56, 2005.
[Journal]
33)  Bibillo A, Lener D, Tewari A, Le Grice SF.
Interaction of the Ty3 reverse transcriptase thumb subdomain with template-primer.
J Biol Chem. 280: 30282-90, 2005.
[Journal]
34)  Shkriabai N, Patil SS, Hess S, Budihas SR, Craigie R, Burke TR, Le Grice SF, Kvaratskhelia M.
Identification of an inhibitor-binding site to HIV-1 integrase with affinity acetylation and mass spectrometry.
Proc Natl Acad Sci U S A. 101: 6894-9, 2004.
[Journal]
35)  Chan KC, Budihas SR, Le Grice SF, Parniak MA, Crouch RJ, Gaidamakov SA, Isaaq HJ, Wamiru A, McMahon JB, Beutler JA.
A capillary electrophoretic assay for ribonuclease H activity.
Anal Biochem. 331: 296-302, 2004.
[Journal]
36)  Rausch JW, Le Grice SF.
'Binding, bending and bonding': polypurine tract-primed initiation of plus-strand DNA synthesis in human immunodeficiency virus.
Int J Biochem Cell Biol. 36: 1752-1766, 2004.
[Journal]
37)  Sitaraman K, Esposito D, Klarmann G, Le Grice SF, Hartley JL, Chatterjee DK.
A novel cell-free protein synthesis system.
J Biotechnol. 110: 257-263, 2004.
[Journal]
38)  Klarmann GJ, Eisenhauer BM, Zhang Y, Sitaraman K, Chatterjee DK, Hecht SM, Le Grice SF.
Site- and subunit-specific incorporation of unnatural amino acids into HIV-1 reverse transcriptase.
Protein Expr Purif. 38: 37-44, 2004.
[Journal]
39)  Miller JT, Khvorova A, Scaringe SA, Le Grice SF.
Synthetic tRNALys,3 as the replication primer for the HIV-1HXB2 and HIV-1Mal genomes.
Nucleic Acids Res. 32: 4687-95, 2004.
[Journal]
40)  Dash C, Yi-Brunozzi HY, Le Grice SF.
Two modes of HIV-1 polypurine tract cleavage are affected by introducing locked nucleic acid analogs into the (-) DNA template.
J Biol Chem. 279: 37095-102, 2004.
[Journal]
41)  Dash C, Rausch JW, Le Grice SF.
Using pyrrolo-deoxycytosine to probe RNA/DNA hybrids containing the human immunodeficiency virus type-1 3' polypurine tract.
Nucleic Acids Res. 32: 1539-47, 2004.
[Journal]
42)  Le Grice SF.
"In the beginning": Initiation of minus strand DNA synthesis in retroviruses and LTR-containing retrotransposons.
Biochemistry. 42: 14349-14355, 2003.
[Journal]
43)  Parniak MA, Min KL, Budihas SR, Le Grice SF, Beutler JA.
A fluorescence-based high-throughput screening assay for inhibitors of human immunodeficiency virus-1 reverse transcriptase-associated ribonuclease H activity.
Anal. Biochem. 322: 33-39, 2003.
[Journal]
44)  Rigourd M, Bec G, Bénas P, Le Grice SF, Ehresmann B, Ehresmann C, Marquet R.
Effects of tRNA(3)(Lys) aminoacylation on the initiation of HIV-1 reverse transcription.
Biochimie. 85: 521-5, 2003.
[Journal]
45)  Post K, Guo J, Howard KJ, Powell MD, Miller JT, Hizi A, Le Grice SF, Levin JG.
Human immunodeficiency virus type 2 reverse transcriptase activity in model systems that mimic steps in reverse transcription.
J Virol. 77: 7623-34, 2003.
[Journal]
46)  Rausch JW, Qu J, Yi-Brunozzi HY, Kool ET, Le Grice SF.
Hydrolysis of RNA/DNA hybrids containing nonpolar pyrimidine isosteres defines regions essential for HIV type 1 polypurine tract selection.
Proc Natl Acad Sci U S A. 100: 11279-11284, 2003.
[Journal]
47)  Lener D, Kvaratskhelia M, Le Grice SF.
Nonpolar thymine isosteres in the Ty3 polypurine tract DNA template modulate processing and provide a model for its recognition by Ty3 reverse transcriptase.
J. Biol. Chem. 278: 26526-26532, 2003.
[Journal]
48)  Roda RH, Balakrishnan M, Hanson MN, Wohrl BM, Le Grice SF, Roques BP, Gorelick RJ, Bambara RA.
Role of the reverse transcriptase, nucleocapsid protein, and template structure in the two-step transfer mechanism in retroviral recombination.
J Biol Chem. 278: 31536-31546, 2003.
[Journal]
49)  Rausch JW, Lener D, Miller JT, Julias JG, Hughes SH, Le Grice SF.
Altering the RNase H primer grip of human immunodeficiency virus reverse transcriptase modifies cleavage specificity.
Biochemistry. 41: 4856-65, 2002.
[Journal]
50)  Goldschmidt V, Rigourd M, Ehresmann C, Le Grice SF, Ehresmann B, Marquet R.
Direct and indirect contributions of RNA secondary structure elements to the initiation of HIV-1 reverse transcription.
J Biol Chem. 277: 43233-43242, 2002.
[Journal]
51)  Moscardini M, Pistello M, Bendinelli M, Ficheux D, Miller JT, Gabus C, Le Grice SF, Surewicz WK, Darlix JL.
Functional interactions of nucleocapsid protein of feline immunodeficiency virus and cellular prion protein with the viral RNA.
J Mol Biol. 318: 149-59, 2002.
[Journal]
52)  Kvaratskhelia M, Miller JT, Budihas SR, Pannell LK, Le Grice SF.
Identification of specific HIV-1 reverse transcriptase contacts to the viral RNA:tRNA complex by mass spectrometry and a primary amine selective reagent.
Proc Natl Acad Sci U S A. 99: 15988-93, 2002.
[Journal]
53)  Lener D, Budihas SR, Le Grice SF.
Mutating conserved residues in the ribonuclease H domain of Ty3 reverse transcriptase affects specialized cleavage events.
J Biol Chem. 277: 26486-95, 2002.
[Journal]
54)  Cristofaro JV, Rausch JW, Le Grice SF, DeStefano JJ.
Mutations in the ribonuclease H active site of HIV-RT reveal a role for this site in stabilizing enzyme-primer-template binding.
Biochemistry. 41: 10968-75, 2002.
[Journal]
55)  Kvaratskhelia M, Budihas SR, Le Grice SF.
Pre-existing distortions in nucleic acid structure aid polypurine tract selection by HIV-1 reverse transcriptase.
J Biol Chem. 277: 16689-96, 2002.
[Journal]
56)  Brulé F, Marquet R, Rong L, Wainberg MA, Roques BP, Le Grice SF, Ehresmann B, Ehresmann C.
Structural and functional properties of the HIV-1 RNA-tRNA(Lys)3 primer complex annealed by the nucleocapsid protein: comparison with the heat-annealed complex.
RNA. 8: 8-15, 2002.
[Journal]
57)  Nymark-McMahon MH, Beliakova-Bethell NS, Darlix JL, Le Grice SF, Sandmeyer SB.
Ty3 integrase is required for initiation of reverse transcription.
J Virol. 76: 2804-16, 2002.
[Journal]
58)  Klarmann GJ, Hawkins ME, Le Grice SF.
Uncovering the complexities of retroviral ribonuclease H reveals its potential as a therapeutic target.
AIDS Rev. 4: 183-94, 2002.
[Journal]
59)  Miller JT, Ehresmann B, Hübscher U, Le Grice SF.
A novel interaction of tRNA(Lys,3) with the feline immunodeficiency virus RNA genome governs initiation of minus strand DNA synthesis.
J Biol Chem. 276: 27721-30, 2001.
[Journal]
60)  Miller JT, Rausch JW, Le Grice SF.
Evaluation of retroviral ribonuclease H activity.
Methods Mol Biol. 160: 335-54, 2001.
[Journal]
61)  Gorshkova II, Rausch JW, Le Grice SF, Crouch RJ.
HIV-1 reverse transcriptase interaction with model RNA-DNA duplexes.
Anal Biochem. 291: 198-206, 2001.
[Journal]
62)  Berdis AJ, Stetor SR, LeGrice SF, Barkley MD.
Molecular mechanism of sequence-specific termination of lentiviral replication.
Biochemistry. 40: 12140-9, 2001.
[Journal]
63)  Lanchy JM, Isel C, Keith G, Le Grice SF, Ehresmann C, Ehresmann B, Marquet R.
Dynamics of the HIV-1 reverse transcription complex during initiation of DNA synthesis.
J Biol Chem. 275: 12306-12, 2000.
[Journal]
64)  Brulé F, Bec G, Keith G, Le Grice SF, Roques BP, Ehresmann B, Ehresmann C, Marquet R.
In vitro evidence for the interaction of tRNA(3)(Lys) with U3 during the first strand transfer of HIV-1 reverse transcription.
Nucleic Acids Res. 28: 634-40, 2000.
[Journal]
65)  Rigourd M, Lanchy JM, Le Grice SF, Ehresmann B, Ehresmann C, Marquet R.
Inhibition of the initiation of HIV-1 reverse transcription by 3'-azido-3'-deoxythymidine. Comparison with elongation.
J Biol Chem. 275: 26944-51, 2000.
[Journal]
66)  Rausch JW, Grice MK, Henrietta M, Nymark-McMahon , Miller JT, Le Grice SF.
Interaction of p55 reverse transcriptase from the Saccharomyces cerevisiae retrotransposon Ty3 with conformationally distinct nucleic acid duplexes.
J Biol Chem. 275: 13879-87, 2000.
[Journal]
67)  Cowan JA, Ohyama T, Howard K, Rausch JW, Cowan SM, Le Grice SF.
Metal-ion stoichiometry of the HIV-1 RT ribonuclease H domain: evidence for two mutually exclusive sites leads to new mechanistic insights on metal-mediated hydrolysis in nucleic acid biochemistry.
J Biol Inorg Chem. 5: 67-74, 2000.
[Journal]
68)  Rausch JW, Sathyanarayana BK, Bona MK, Le Grice SF.
Probing contacts between the ribonuclease H domain of HIV-1 reverse transcriptase and nucleic acid by site-specific photocross-linking.
J Biol Chem. 275: 16015-22, 2000.
[Journal]
69)  Beutler J, Le Grice S, Parniak M, Budihas S, Wamiru A, Gardella R, Wilson J, Gonchorova K, inventor; DHHS, assignee.
Inhibition Of HIV Using Rnase H Inhibitors.
Patent Pending, Filed in 2004. Application No. 11/660,259. Pending [Patent]

This page was last updated on 1/20/2009.