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Matthias Götte

Professor;
Biochemical Virology

Matthias Gotte

Lyman Duff Medical Building
3775 University St., Room D6
Montreal, QC H3A 2B4
Tel: (514) 398-1365
Fax: (514) 398-7052
matthias [dot] gotte [at] mcgill [dot] ca 

Research Orientations

Research in his group is focused on structure-function relationships of viral enzymes, with emphasis placed on mechanisms involved in drug action and drug resistance. The reverse transcriptase (RT) of HIV-1, the RNA-dependent RNA polymerase and helicase of the hepatitis C virus (HCV), and herpes virus DNA polymerases are major themes. The lab is actively involved in the development of novel classes of compounds that block the DNA polymerase activity of wild-type HIV-1 RT and its resistant variants.

Selected Recent Publications

Zahn KE, Tchesnokov EP, Gotte M, Doublie S. Phosphonoformic acid inhibits viral replication by trapping the closed form of the DNA polymerase. J Biol Chem. 2011 May 12. [Epub ahead of print] 

Scarth BJ, White KL, Chen JM, Lansdon EB, Swaminathan S, Miller MD, Götte M. Mechanism of resistance to GS-9148 by the Q151L mutation in HIV-1 Reverse Transcriptase. Antimicrob Agents Chemother. 2011 Jun;55(6):2662-9.

Scarth B, McCormick S, Götte M. Effects of mutations F61A and A62V in the fingers subdomain of HIV-1 reverse transcriptase on the translocational equilibrium. J Mol Biol. 2011 Jan 14;504(2):349-60.

Biondi MJ, Beilhartz GL, McCormick S, Götte M. N348I in HIV-1 reverse transcriptase can counteract the nevirapine-mediated bias toward RNase H cleavage during plus-strand initiation. J Biol Chem. 2010 Aug 27;285(35):36966-75.

von Wyl V, Ehteshami M, Symons J, Bürgisser P, Nijhuis M, Demeter LM, Yerly S, Bôni J, Klimkait T, Schuuman R, Ledergerber B, Gôtte M. Günthard HF. Swiss HIV Cohort Study Epidemiological and biological evidence for a compensatory effect of connection domain mutation N348I on M184V in HIV-1 reverse transcriptase. J Infect Dis. 2010 Apr1:201(7): 1054-62.

Powdrill MH, Devval J, Narjes F, De Francesco R, Gôtte M. Mechanism of hepatitis C virus RNA polymerase inhibition with dihydroxypyrimidines. Antimicrob Agents Chemother 2010 Mar.54(3):977-83. Epub 2009 Dec 22.

Götte M, Rausch JW, Marchand B, Sarafianos S, Le Grice SF. Reverse transcriptase in motion: Conformational dynamics of enzyme-substrate interactions. Biochim Biophys Acta. 2009 Aug 6. [Epub ahead of print]

Tchesnokov EP, Obikhod A, Schinazi RF, Götte M*. Engineering of a chimeric RB69 DNA polymerase sensitive to drugs targeting the cytomegalovirus enzyme. J Biol Chem. 2009 Jul 21. [Epub ahead of print]

Tchesnokov EP, Obikhod A, Massud I, Lisco A, Vanpouille C, Brichacek B, Balzarini J, McGuigan C, Derudas M, Margolis L, Schinazi RF, Götte M*. Mechanisms Associated with HIV-1 Resistance to Acyclovir by the V75I Mutation in Reverse Transcriptase. J Biol Chem. 2009 Aug 7;284(32):21496-504.

Beilhartz GL, Wendeler M, Baichoo N, Rausch J, Le Grice S, Götte M* "HIV-1 Reverse Transcriptase Can Simultaneously Engage its DNA/RNA Substrate at the DNA Polymerase and RNase H Active Sites: Implications for RNase H Inhibition." J Mol Biol. 2009 May 8;388(3):462-74

Castro C, Smidansky ED, Arnold JJ, Maksimchuk KR, Moustafa I, Uchida A, Götte M, Konigsberg W, Cameron CE "Nucleic acid polymerases employ a general acid for nucleotidyl transfer." Nat Struct Mol Biol. 2009 Feb;16(2):212-8

Ehteshami M, Götte M*. "Effects of mutations in the connection and RNase H domains of HIV-1 reverse transcriptase on drug susceptibility." AIDS Rev. 2008 Oct-Dec;10(4):224-35, Review

Tchesnokov EP, Obikhod A, Schinazi RF, Götte M*. "Delayed chain termination protects the anti-hepatitis B virus drug entecavir from excision by HIV-1 reverse transcriptase." J Biol Chem. 2008 Dec 5;283(49):34218-28

Lisco A, Vanpouille C, Tchesnokov EP, Grivel JC, Biancotto A, Brichacek B, Elliott J, Fromentin E, Shattock R, Anton P, Gorelick R, Balzarini J, McGuigan C, Derudas M, Götte M, Schinazi RF, Margolis L. "Acyclovir is activated into a HIV-1 reverse transcriptase inhibitor in herpesvirus-infected human tissues." Cell Host Microbe. 2008 Sep 11;4(3):260-70.

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 Oct 31;283(44):29904-11. Epub 2008 Aug 25.

Ehteshami M, Beilhartz GL, Scarth BJ, Tchesnokov EP, McCormick S, Wynhoven B, Harrigan PR, Götte M*. "Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3'-azido-3'-deoxythymidine through both RNase H-dependent and -independent mechanisms." J Biol Chem. 2008 Aug 8;283(32):22222-32. Epub 2008 Jun 10.

Götte M*. "Should we include connection domain mutations of HIV-1 reverse transcriptase in HIV resistance testing?" PLoS Med. 2007 Dec;4(12), Perspective

Marchand B, White KL, Ly JK, Margot NA, Wang R, McDermott M, Miller MD, Götte M* "Effects of the Translocation Status of HIV-1 Reverse Transcriptase on the efficiency of excision of tenofovir." Antimicrob Agents Chemother. 2007 Aug;51(8):2911-9.

Deval J, Powdrill MH, D'Abramo CM, Cellai L, Götte M*. "Pyrophosphorolytic Excision of non-obligate chain-terminators by Hepatitis C Virus NS5B Polymerase." Antimicrob Agents Chemother. 2007 Aug;51(8):2920-8.

Deval J, D'Abramo CM, Zhao Z, McCormick S, Coutsinos D, Hess S, Kvaratskhelia M, Götte M* "High Resolution Footprinting of the Hepatitis C Virus Polymerase NS5B in Complex with RNA." J Biol Chem. 2007 Jun 8;282(23):16907-16.

Marchand B, Tchesnokov EP, Götte M.* "The Pyrophosphate Analogue Foscarnet Traps the Pre-translocated state of HIV-1 Reverse Transcriptase in a Brownian Ratchet Model of Translocation." J Biol Chem. 2007 Feb 2;282(5):3337-46.

Jochmans D, Deval J, Kesteleyn B, Van Marck H, Bettens E, De Baere I, Dehertogh P, Ivens T, Van Ginderen M, Van Schoubroeck B, Ehteshami M, Wigerinck P, Götte M, Hertogs K "Indolopyridones Inhibit HIV Reverse Transcriptase with a Novel Mechanism of Action." J Virol. 2006 Dec;80(24):12283-92.

D'Abramo CM, Deval J, Cameron CE, Cellai L, Götte M*. "Control of template positioning during De Novo initiation of RNA synthesis by the BVDV NS5B polymerase." J Biol Chem. 2006 Aug 25;281(34):24991-8.

Tchesnokov EP, Gilbert C, Boivin G, Götte M* "Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to foscarnet." J Virol. 2006 Feb;80(3):1440-50.

Götte M* "Effects of Nucleotides and Nucleotide Analogue Inhibitors in a Ratchet Model of HIV-1 Reverse Transcriptase Translocation." Curr Pharm Des. 2006;12(15):1867-77; Review