Faculty Appointments
Professor of Biochemistry
Education
Ph.D., Organic Chemistry, ETH-Zurich , Zurich , SwitzerlandB.S., Chemistry, ETH-Zurich , Zurich , Switzerland
Office Address
868A RRB
Nashville, KY 37232
Nashville, KY 37232
Research Description
On-going efforts in my laboratory focus on the following areas. (i) Structure/function analyses of native and chemically modified nucleic acids and etiology of nucleic acid structure. Using chemical synthesis and structure determination at high resolution, the effects of chemical modifications on the structures of DNA and RNA are examined and the results correlated with stability and in vitro and in vivo activity data to direct the design of nucleic acid analogs with improved efficacies for antisense and RNAi applications. We are collaborating with researchers from Alnylam Pharmaceuticals Inc. (Cambridge, MA) and Isis Pharmaceuticals Inc. (Carlsbad, CA) to exploit insights from structural studies for the design of next generation antisense and siRNA therapeutics. (ii) Chemistry and biology of carcinogen-DNA adducts. This program examines relationships between the structure and biological processing of damaged bases by Y-class trans-lesion DNA polymerases (i.e. Dpo4 from Sulfolobus solfataricus and human Pol-iota, Pol-kappa and Pol-eta). Using in vitro primer extension assays in combination with steady state and pre-steady state kinetics as well as mass spectrometry, we are probing the effects on the accuracy of replication of a range of adducts inside the template strand (8-oxo-dG, O6-methyl-dG, N2-methyl-dG, 1,N2-etheno-dG, acrolein, cyclic pyrimidine dimers and others). Crystal structures of binary Pol-DNA and ternary Pol-DNA-dNTP complexes are determined to shed light on the consequences of individual lesions for the accuracy of bypass. (iii) The cyanobacterial KaiABC circadian clock. The circadian clock of Synechococcus elongatus can be reconstituted in vitro with the three proteins KaiA, KaiB and KaiC in the presence of ATP and Mg2+. KaiC is the central cog and exhibits kinase, phosphatase and ATPase activities, KaiA enhances KaiC phosphorylation and KaiB antagonizes KaiA. Remarkably, this post-translational timer exhibits all the hallmarks of circadian clocks - a period of ca. 24 hours, entrainment and temperature compensation - thus permitting its dissection by biochemical and biophysical means. Using a hybrid structural approach including single crystal X-ray crystallography, electron microscopy and small angle X-ray and neutron scattering in combination with functional studies in vitro and in vivo, we are analyzing the protein-protein interactions and mechanistic aspects of this molecular clock.
Research Keywords
Structural Biology of Circadian Clocks, native and
chemically modified nucleic acids, and trans-lesion DNA polymerase-DNA
adduct interactions
Publications
Wang Y, Musser SK, Saleh S, Marnett LJ, Egli M, Stone MP. Insertion of dNTPs opposite the 1,N2-propanodeoxyguanosine adduct by Sulfolobus solfataricus P2 DNA polymerase IV. Biochemistry [print-electronic]. 2008 Jul 7/15/2008; 47(28): 7322-34. PMID: 18563918, PMCID: PMC2753402, DOI: 10.1021/bi800152j, ISSN: 1520-4995.
Wang F, Li F, Ganguly M, Marky LA, Gold B, Egli M, Stone MP. A bridging water anchors the tethered 5-(3-aminopropyl)-2'-deoxyuridine amine in the DNA major groove proximate to the N+2 C.G base pair: implications for formation of interstrand 5'-GNC-3' cross-links by nitrogen mustards. Biochemistry [print-electronic]. 2008 Jul 7/8/2008; 47(27): 7147-57. PMID: 18549246, PMCID: PMC2730145, DOI: 10.1021/bi800375m, ISSN: 1520-4995.
Pattanayek R, Williams DR, Pattanayek S, Mori T, Johnson CH, Stewart PL, Egli M. Structural model of the circadian clock KaiB-KaiC complex and mechanism for modulation of KaiC phosphorylation. EMBO J [print-electronic]. 2008 Jun 6/18/2008; 27(12): 1767-78. PMID: 18497745, PMCID: PMC2435126, PII: emboj2008104, DOI: 10.1038/emboj.2008.104, ISSN: 1460-2075.
Pallan PS, Ittig D, Héroux A, Wawrzak Z, Leumann CJ, Egli M. Crystal structure of tricyclo-DNA: an unusual compensatory change of two adjacent backbone torsion angles. Chem. Commun. (Camb.) [print-electronic]. 2008 Feb 2/21/2008; (7): 883-5. PMID: 18253536, DOI: 10.1039/b716390h, ISSN: 1359-7345.
Irimia A, Eoff RL, Pallan PS, Guengerich FP, Egli M. Structure and activity of Y-class DNA polymerase DPO4 from Sulfolobus solfataricus with templates containing the hydrophobic thymine analog 2,4-difluorotoluene. J. Biol. Chem [print-electronic]. 2007 Dec 12/14/2007; 282(50): 36421-33. PMID: 17951245, PII: M707267200, DOI: 10.1074/jbc.M707267200, ISSN: 0021-9258.
Eoff RL, Irimia A, Angel KC, Egli M, Guengerich FP. Hydrogen bonding of 7,8-dihydro-8-oxodeoxyguanosine with a charged residue in the little finger domain determines miscoding events in Sulfolobus solfataricus DNA polymerase Dpo4. J. Biol. Chem [print-electronic]. 2007 Jul 7/6/2007; 282(27): 19831-43. PMID: 17468100, PII: M702290200, DOI: 10.1074/jbc.M702290200, ISSN: 0021-9258.
Eoff RL, Angel KC, Egli M, Guengerich FP. Molecular basis of selectivity of nucleoside triphosphate incorporation opposite O6-benzylguanine by sulfolobus solfataricus DNA polymerase Dpo4: steady-state and pre-steady-state kinetics and x-ray crystallography of correct and incorrect pairing. J. Biol. Chem [print-electronic]. 2007 May 5/4/2007; 282(18): 13573-84. PMID: 17337730, PII: M700656200, DOI: 10.1074/jbc.M700656200, ISSN: 0021-9258.
Pallan PS, Lubini P, Egli M. A left-handed supramolecular assembly around a right-handed screw axis in the crystal structure of homo-DNA. Chem. Commun. (Camb.) [print-electronic]. 2007 Apr 4/14/2007; (14): 1447-9. PMID: 17389988, DOI: 10.1039/b614983a, ISSN: 1359-7345.
Mori T, Williams DR, Byrne MO, Qin X, Egli M, Mchaourab HS, Stewart PL, Johnson CH. Elucidating the ticking of an in vitro circadian clockwork. PLoS Biol. 2007 Apr; 5(4): e93. PMID: 17388688, PMCID: PMC1831719, PII: 06-PLBI-RA-2188R2, DOI: 10.1371/journal.pbio.0050093, ISSN: 1545-7885.
Egli M, Sarkhel S. Lone pair-aromatic interactions: to stabilize or not to stabilize. Acc. Chem. Res. 2007 Mar; 40(3): 197-205. PMID: 17370991, DOI: 10.1021/ar068174u, ISSN: 0001-4842.
Luka Z, Pakhomova S, Loukachevitch LV, Egli M, Newcomer ME, Wagner C. 5-methyltetrahydrofolate is bound in intersubunit areas of rat liver folate-binding protein glycine N-methyltransferase. J. Biol. Chem [print-electronic]. 2007 Feb 2/9/2007; 282(6): 4069-75. PMID: 17158459, PII: M610384200, DOI: 10.1074/jbc.M610384200, ISSN: 0021-9258.
Loukachevitch LV, Egli M. Crystallization and preliminary X-ray analysis of Escherichia coli RNase HI-dsRNA complexes. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun [print-electronic]. 2007 Feb 2/1/2007; 63(Pt 2): 84-8. PMID: 17277445, PMCID: PMC2330121, PII: S1744309106055461, DOI: 10.1107/S1744309106055461, ISSN: 1744-3091.
Eoff RL, Irimia A, Egli M, Guengerich FP. Sulfolobus solfataricus DNA polymerase Dpo4 is partially inhibited by "wobble" pairing between O6-methylguanine and cytosine, but accurate bypass is preferred. J. Biol. Chem [print-electronic]. 2007 Jan 1/12/2007; 282(2): 1456-67. PMID: 17105728, PII: M609661200, DOI: 10.1074/jbc.M609661200, ISSN: 0021-9258.
Pallan PS, Egli M. Selenium modification of nucleic acids: preparation of oligonucleotides with incorporated 2'-SeMe-uridine for crystallographic phasing of nucleic acid structures. Nat Protoc. 2007; 2(3): 647-51. PMID: 17406626, PII: nprot.2007.75, DOI: 10.1038/nprot.2007.75, ISSN: 1750-2799.
Pallan PS, Egli M. Selenium modification of nucleic acids: preparation of phosphoroselenoate derivatives for crystallographic phasing of nucleic acid structures. Nat Protoc. 2007; 2(3): 640-6. PMID: 17406625, PII: nprot.2007.74, DOI: 10.1038/nprot.2007.74, ISSN: 1750-2799.
Egli M, Pallan PS. Insights from crystallographic studies into the structural and pairing properties of nucleic acid analogs and chemically modified DNA and RNA oligonucleotides. Annu Rev Biophys Biomol Struct. 2007; 36: 281-305. PMID: 17288535, DOI: 10.1146/annurev.biophys.36.040306.132556, ISSN: 1056-8700.
Egli M, Lubini P, Pallan PS. The long and winding road to the structure of homo-DNA. Chem Soc Rev [print-electronic]. 2007 Jan; 36(1): 31-45. PMID: 17173143, DOI: 10.1039/b606807c, ISSN: 0306-0012.
Pallan PS, Lubini P, Bolli M, Egli M. Backbone-base inclination as a fundamental determinant of nucleic acid self- and cross-pairing. Nucleic Acids Res [print-electronic]. 2007; 35(19): 6611-24. PMID: 17905816, PMCID: PMC2095819, PII: gkm612, DOI: 10.1093/nar/gkm612, ISSN: 1362-4962.
Li F, Pallan PS, Maier MA, Rajeev KG, Mathieu SL, Kreutz C, Fan Y, Sanghvi J, Micura R, Rozners E, Manoharan M, Egli M. Crystal structure, stability and in vitro RNAi activity of oligoribonucleotides containing the ribo-difluorotoluyl nucleotide: insights into substrate requirements by the human RISC Ago2 enzyme. Nucleic Acids Res [print-electronic]. 2007; 35(19): 6424-38. PMID: 17881374, PMCID: PMC2095806, PII: gkm664, DOI: 10.1093/nar/gkm664, ISSN: 1362-4962.
Egli M, Pallan PS, Pattanayek R, Wilds CJ, Lubini P, Minasov G, Dobler M, Leumann CJ, Eschenmoser A. Crystal structure of homo-DNA and nature's choice of pentose over hexose in the genetic system. J. Am. Chem. Soc. 2006 Aug 8/23/2006; 128(33): 10847-56. PMID: 16910680, DOI: 10.1021/ja062548x, ISSN: 0002-7863.
Pallan PS, von Matt P, Wilds CJ, Altmann KH, Egli M. RNA-Binding affinities and crystal structure of oligonucleotides containing five-atom amide-based backbone structures. Biochemistry. 2006 Jul 7/4/2006; 45(26): 8048-57. PMID: 16800629, DOI: 10.1021/bi060354o, ISSN: 0006-2960.
Irimia A, Zang H, Loukachevitch LV, Eoff RL, Guengerich FP, Egli M. Calcium is a cofactor of polymerization but inhibits pyrophosphorolysis by the Sulfolobus solfataricus DNA polymerase Dpo4. Biochemistry. 2006 May 5/16/2006; 45(19): 5949-56. PMID: 16681366, DOI: 10.1021/bi052511+, ISSN: 0006-2960.
Pattanayek R, Williams DR, Pattanayek S, Xu Y, Mori T, Johnson CH, Stewart PL, Egli M. Analysis of KaiA-KaiC protein interactions in the cyano-bacterial circadian clock using hybrid structural methods. EMBO J [print-electronic]. 2006 May 5/3/2006; 25(9): 2017-28. PMID: 16628225, PMCID: PMC1456936, PII: 7601086, DOI: 10.1038/sj.emboj.7601086, ISSN: 0261-4189.
Xia J, Noronha A, Toudjarska I, Li F, Akinc A, Braich R, Frank-Kamenetsky M, Rajeev KG, Egli M, Manoharan M. Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide. ACS Chem. Biol. 2006 Apr 4/25/2006; 1(3): 176-83. PMID: 17163665, DOI: 10.1021/cb600063p, ISSN: 1554-8937.
Li F, Sarkhel S, Wilds CJ, Wawrzak Z, Prakash TP, Manoharan M, Egli M. 2'-Fluoroarabino- and arabinonucleic acid show different conformations, resulting in deviating RNA affinities and processing of their heteroduplexes with RNA by RNase H. Biochemistry. 2006 Apr 4/4/2006; 45(13): 4141-52. PMID: 16566588, PMCID: PMC2553321, DOI: 10.1021/bi052322r, ISSN: 0006-2960.
Zang H, Irimia A, Choi JY, Angel KC, Loukachevitch LV, Egli M, Guengerich FP. Efficient and high fidelity incorporation of dCTP opposite 7,8-dihydro-8-oxodeoxyguanosine by Sulfolobus solfataricus DNA polymerase Dpo4. J. Biol. Chem [print-electronic]. 2006 Jan 1/27/2006; 281(4): 2358-72. PMID: 16306039, PII: M510889200, DOI: 10.1074/jbc.M510889200, ISSN: 0021-9258.
Pallan PS, Marshall WS, Harp J, Jewett FC, Wawrzak Z, Brown BA, Rich A, Egli M. Crystal structure of a luteoviral RNA pseudoknot and model for a minimal ribosomal frameshifting motif. Biochemistry. 2005 Aug 8/30/2005; 44(34): 11315-22. PMID: 16114868, PMCID: PMC2556298, DOI: 10.1021/bi051061i, ISSN: 0006-2960.
Zang H, Goodenough AK, Choi JY, Irimia A, Loukachevitch LV, Kozekov ID, Angel KC, Rizzo CJ, Egli M, Guengerich FP. DNA adduct bypass polymerization by Sulfolobus solfataricus DNA polymerase Dpo4: analysis and crystal structures of multiple base pair substitution and frameshift products with the adduct 1,N2-ethenoguanine. J. Biol. Chem [print-electronic]. 2005 Aug 8/19/2005; 280(33): 29750-64. PMID: 15965231, PII: M504756200, DOI: 10.1074/jbc.M504756200, ISSN: 0021-9258.
Egli M, Minasov G, Tereshko V, Pallan PS, Teplova M, Inamati GB, Lesnik EA, Owens SR, Ross BS, Prakash TP, Manoharan M. Probing the influence of stereoelectronic effects on the biophysical properties of oligonucleotides: comprehensive analysis of the RNA affinity, nuclease resistance, and crystal structure of ten 2'-O-ribonucleic acid modifications. Biochemistry. 2005 Jun 6/28/2005; 44(25): 9045-57. PMID: 15966728, DOI: 10.1021/bi050574m, ISSN: 0006-2960.
Diop-Frimpong B, Prakash TP, Rajeev KG, Manoharan M, Egli M. Stabilizing contributions of sulfur-modified nucleotides: crystal structure of a DNA duplex with 2'-O-[2-(methoxy)ethyl]-2-thiothymidines. Nucleic Acids Res [electronic-print]. 2005; 33(16): 5297-307. PMID: 16170156, PMCID: PMC1216336, PII: 33/16/5297, DOI: 10.1093/nar/gki823, ISSN: 1362-4962.
Haeberli P, Berger I, Pallan PS, Egli M. Syntheses of 4'-thioribonucleosides and thermodynamic stability and crystal structure of RNA oligomers with incorporated 4'-thiocytosine. Nucleic Acids Res [electronic-print]. 2005; 33(13): 3965-75. PMID: 16027443, PMCID: PMC1178003, PII: 33/13/3965, DOI: 10.1093/nar/gki704, ISSN: 1362-4962.
Egli M. Nucleic acid crystallography: current progress. Curr Opin Chem Biol. 2004 Dec; 8(6): 580-91. PMID: 15556400, PII: S1367-5931(04)00128-0, DOI: 10.1016/j.cbpa.2004.09.004, ISSN: 1367-5931.
Pattanayek R, Sethaphong L, Pan C, Prhavc M, Prakash TP, Manoharan M, Egli M. Structural rationalization of a large difference in RNA affinity despite a small difference in chemistry between two 2'-O-modified nucleic acid analogues. J. Am. Chem. Soc. 2004 Nov 11/24/2004; 126(46): 15006-7. PMID: 15547979, DOI: 10.1021/ja044637k, ISSN: 0002-7863.
Xu Y, Mori T, Pattanayek R, Pattanayek S, Egli M, Johnson CH. Identification of key phosphorylation sites in the circadian clock protein KaiC by crystallographic and mutagenetic analyses. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2004 Sep 9/21/2004; 101(38): 13933-8. PMID: 15347809, PMCID: PMC518856, PII: 0404768101, DOI: 10.1073/pnas.0404768101, ISSN: 0027-8424.
Pattanayek R, Wang J, Mori T, Xu Y, Johnson CH, Egli M. Visualizing a circadian clock protein: crystal structure of KaiC and functional insights. Mol. Cell. 2004 Aug 8/13/2004; 15(3): 375-88. PMID: 15304218, PII: S1097276504004356, DOI: 10.1016/j.molcel.2004.07.013, ISSN: 1097-2765.
Egli M. "Deoxyribo nanonucleic acid"; antiparallel, parallel, and unparalleled. Chem. Biol. 2004 Aug; 11(8): 1027-9. PMID: 15324800, PII: S107455210400211X, DOI: 10.1016/j.chembiol.2004.08.002, ISSN: 1074-5521.
Cook S, Hugli O, Egli M, Ménard B, Thalmann S, Sartori C, Perrin C, Nicod P, Thorens B, Vollenweider P, Scherrer U, Burcelin R. Partial gene deletion of endothelial nitric oxide synthase predisposes to exaggerated high-fat diet-induced insulin resistance and arterial hypertension. Diabetes. 2004 Aug; 53(8): 2067-72. PMID: 15277387, PII: 53/8/2067, ISSN: 0012-1797.
Johnson CH, Egli M. Visualizing a biological clockwork's cogs. Nature structural & molecular biology. 2004 Jul; 11(7) Sect. 584,5.
Prakash TP, Püschl A, Lesnik E, Mohan V, Tereshko V, Egli M, Manoharan M. 2'-O-[2-(guanidinium)ethyl]-modified oligonucleotides: stabilizing effect on duplex and triplex structures. Org. Lett. 2004 Jun 6/10/2004; 6(12): 1971-4. PMID: 15176796, DOI: 10.1021/ol049470e, ISSN: 1523-7060.
Egli M, Tereshko V, Mushudov GN, Sanishvili R, Liu X, Lewis FD. Face-to-face and edge-to-face pi-pi interactions in a synthetic DNA hairpin with a stilbenediether linker. J. Am. Chem. Soc. 2003 Sep 9/10/2003; 125(36): 10842-9. PMID: 12952463, DOI: 10.1021/ja0355527, ISSN: 0002-7863.
Sarkhel S, Rich A, Egli M. Water-nucleobase "stacking": H-pi and lone pair-pi interactions in the atomic resolution crystal structure of an RNA pseudoknot. J. Am. Chem. Soc. 2003 Jul 7/30/2003; 125(30): 8998-9. PMID: 15369340, DOI: 10.1021/ja0357801, ISSN: 0002-7863.
Pallan PS, Wilds CJ, Wawrzak Z, Krishnamurthy R, Eschenmoser A, Egli M. Why does TNA cross-pair more strongly with RNA than with DNA? an answer from X-ray analysis. Angew. Chem. Int. Ed. Engl. 2003; 42(47): 5893-5. PMID: 14673929, DOI: 10.1002/anie.200352553, ISSN: 1433-7851.
Wilds CJ, Pattanayek R, Pan C, Wawrzak Z, Egli M. Selenium-assisted nucleic acid crystallography: use of phosphoroselenoates for MAD phasing of a DNA structure. J. Am. Chem. Soc. 2002 Dec 12/18/2002; 124(50): 14910-6. PMID: 12475332, PII: ja021058b, ISSN: 0002-7863.
Wilds CJ, Wawrzak Z, Krishnamurthy R, Eschenmoser A, Egli M. Crystal structure of a B-form DNA duplex containing (L)-alpha-threofuranosyl (3'-->2') nucleosides: a four-carbon sugar is easily accommodated into the backbone of DNA. J. Am. Chem. Soc. 2002 Nov 11/20/2002; 124(46): 13716-21. PMID: 12431101, PII: ja0207807, ISSN: 0002-7863.
Teplova M, Wilds CJ, Wawrzak Z, Tereshko V, Du Q, Carrasco N, Huang Z, Egli M. Covalent incorporation of selenium into oligonucleotides for X-ray crystal structure determination via MAD: proof of principle. Multiwavelength anomalous dispersion. Biochimie. 2002 Sep; 84(9): 849-58. PMID: 12458077, PII: S0300908402014402, ISSN: 0300-9084.
Egli M, Minasov G, Su L, Rich A. Metal ions and flexibility in a viral RNA pseudoknot at atomic resolution. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2002 Apr 4/2/2002; 99(7): 4302-7. PMID: 11904368, PMCID: PMC123643, PII: 062055599, DOI: 10.1073/pnas.062055599, ISSN: 0027-8424.
Egli M. DNA-cation interactions: quo vadis?. Chem. Biol. 2002 Mar; 9(3): 277-86. PMID: 11927253, PII: S1074552102001163, ISSN: 1074-5521.
Joseph B, Egli M, Koppekin A, Thompson T. Food choice in people with Prader-Willi syndrome: quantity and relative preference. Am J Ment Retard. 2002 Mar; 107(2): 128-35. PMID: 11853530, DOI: 10.1352/0895-8017(2002)107<0128:FCIPWP>2.0.CO;2, ISSN: 0895-8017.
Wilds CJ, Maier MA, Tereshko V, Manoharan M, Egli M. Direct observation of a cytosine analogue that forms five hydrogen bonds to guanosine: guanidino G-clamp. Angew. Chem. Int. Ed. Engl. 2002 Jan 1/4/2002; 41(1): 115-7. PMID: 12491456, PII: 10.1002/1521-3773(20020104)41:1<115::AID-ANIE115>3.0.CO;2-R, ISSN: 1433-7851.
Tereshko V, Teplova M, Brunzelle J, Watterson DM, Egli M. Crystal structures of the catalytic domain of human protein kinase associated with apoptosis and tumor suppression. Nat. Struct. Biol. 2001 Oct; 8(10): 899-907. PMID: 11573098, PII: nsb1001-899, DOI: 10.1038/nsb1001-899, ISSN: 1072-8368.
Wilds CJ, Minasov G, Natt F, von Matt P, Altmann KH, Egli M. Studies of a chemically modified oligodeoxynucleotide containing a 5-atom amide backbone which exhibits improved binding to RNA. Nucleosides Nucleotides Nucleic Acids. 2001 Apr; 20(4-7): 991-4. PMID: 11563161, DOI: 10.1081/NCN-100002475, ISSN: 1525-7770.
Tereshko V, Wallace ST, Usman N, Wincott FE, Egli M. X-ray crystallographic observation of "in-line" and "adjacent" conformations in a bulged self-cleaving RNA/DNA hybrid. RNA. 2001 Mar; 7(3): 405-20. PMID: 11333021, PMCID: PMC1370097, ISSN: 1355-8382.
Tereshko V, Wilds CJ, Minasov G, Prakash TP, Maier MA, Howard A, Wawrzak Z, Manoharan M, Egli M. Detection of alkali metal ions in DNA crystals using state-of-the-art X-ray diffraction experiments. Nucleic Acids Res. 2001 Mar 3/1/2001; 29(5): 1208-15. PMID: 11222771, PMCID: PMC29719, ISSN: 1362-4962.
Joseph B, Egli M, Sutcliffe JS, Thompson T. Possible dosage effect of maternally expressed genes on visual recognition memory in Prader-Willi syndrome. Am. J. Med. Genet. 2001 Jan 1/8/2001; 105(1): 71-5. PMID: 11425004, PII: 10.1002/1096-8628(20010108)105:1<71::AID-AJMG1065>3.0.CO;2-8, ISSN: 0148-7299.
Teplova M, Tereshko V, Sanishvili R, Joachimiak A, Bushueva T, Anderson WF, Egli M. The structure of the yrdC gene product from Escherichia coli reveals a new fold and suggests a role in RNA binding. Protein Sci. 2000 Dec; 9(12): 2557-66. PMID: 11206077, PMCID: PMC2144518, DOI: 10.1110/ps.9.12.2557, ISSN: 0961-8368.
Sachdev RN, Egli M, Stonecypher M, Wiley RG, Ebner FF. Enhancement of cortical plasticity by behavioral training in acetylcholine-depleted adult rats. J. Neurophysiol. 2000 Oct; 84(4): 1971-81. PMID: 11024090, ISSN: 0022-3077.
Egli M, Roper T, Feurer I, Thompson T. Architectural acoustics in residences for adults with mental retardation and its relation to perceived homelikeness. Am J Ment Retard. 1999 Jan; 104(1): 53-66. PMID: 9972834, DOI: 10.1352/0895-8017(1999)104<0053:AAIRFA>2.0.CO;2, ISSN: 0895-8017.
Egli M, Joseph B, Thompson T. Transfer of social attributions in stimulus equivalence classes by preschool children. Psychol Rep. 1997 Feb; 80(1): 3-21. PMID: 9122341, DOI: 10.2466/pr0.1997.80.1.3, ISSN: 0033-2941.
Wang F, Li F, Ganguly M, Marky LA, Gold B, Egli M, Stone MP. A bridging water anchors the tethered 5-(3-aminopropyl)-2'-deoxyuridine amine in the DNA major groove proximate to the N+2 C.G base pair: implications for formation of interstrand 5'-GNC-3' cross-links by nitrogen mustards. Biochemistry [print-electronic]. 2008 Jul 7/8/2008; 47(27): 7147-57. PMID: 18549246, PMCID: PMC2730145, DOI: 10.1021/bi800375m, ISSN: 1520-4995.
Pattanayek R, Williams DR, Pattanayek S, Mori T, Johnson CH, Stewart PL, Egli M. Structural model of the circadian clock KaiB-KaiC complex and mechanism for modulation of KaiC phosphorylation. EMBO J [print-electronic]. 2008 Jun 6/18/2008; 27(12): 1767-78. PMID: 18497745, PMCID: PMC2435126, PII: emboj2008104, DOI: 10.1038/emboj.2008.104, ISSN: 1460-2075.
Pallan PS, Ittig D, Héroux A, Wawrzak Z, Leumann CJ, Egli M. Crystal structure of tricyclo-DNA: an unusual compensatory change of two adjacent backbone torsion angles. Chem. Commun. (Camb.) [print-electronic]. 2008 Feb 2/21/2008; (7): 883-5. PMID: 18253536, DOI: 10.1039/b716390h, ISSN: 1359-7345.
Irimia A, Eoff RL, Pallan PS, Guengerich FP, Egli M. Structure and activity of Y-class DNA polymerase DPO4 from Sulfolobus solfataricus with templates containing the hydrophobic thymine analog 2,4-difluorotoluene. J. Biol. Chem [print-electronic]. 2007 Dec 12/14/2007; 282(50): 36421-33. PMID: 17951245, PII: M707267200, DOI: 10.1074/jbc.M707267200, ISSN: 0021-9258.
Eoff RL, Irimia A, Angel KC, Egli M, Guengerich FP. Hydrogen bonding of 7,8-dihydro-8-oxodeoxyguanosine with a charged residue in the little finger domain determines miscoding events in Sulfolobus solfataricus DNA polymerase Dpo4. J. Biol. Chem [print-electronic]. 2007 Jul 7/6/2007; 282(27): 19831-43. PMID: 17468100, PII: M702290200, DOI: 10.1074/jbc.M702290200, ISSN: 0021-9258.
Eoff RL, Angel KC, Egli M, Guengerich FP. Molecular basis of selectivity of nucleoside triphosphate incorporation opposite O6-benzylguanine by sulfolobus solfataricus DNA polymerase Dpo4: steady-state and pre-steady-state kinetics and x-ray crystallography of correct and incorrect pairing. J. Biol. Chem [print-electronic]. 2007 May 5/4/2007; 282(18): 13573-84. PMID: 17337730, PII: M700656200, DOI: 10.1074/jbc.M700656200, ISSN: 0021-9258.
Pallan PS, Lubini P, Egli M. A left-handed supramolecular assembly around a right-handed screw axis in the crystal structure of homo-DNA. Chem. Commun. (Camb.) [print-electronic]. 2007 Apr 4/14/2007; (14): 1447-9. PMID: 17389988, DOI: 10.1039/b614983a, ISSN: 1359-7345.
Mori T, Williams DR, Byrne MO, Qin X, Egli M, Mchaourab HS, Stewart PL, Johnson CH. Elucidating the ticking of an in vitro circadian clockwork. PLoS Biol. 2007 Apr; 5(4): e93. PMID: 17388688, PMCID: PMC1831719, PII: 06-PLBI-RA-2188R2, DOI: 10.1371/journal.pbio.0050093, ISSN: 1545-7885.
Egli M, Sarkhel S. Lone pair-aromatic interactions: to stabilize or not to stabilize. Acc. Chem. Res. 2007 Mar; 40(3): 197-205. PMID: 17370991, DOI: 10.1021/ar068174u, ISSN: 0001-4842.
Luka Z, Pakhomova S, Loukachevitch LV, Egli M, Newcomer ME, Wagner C. 5-methyltetrahydrofolate is bound in intersubunit areas of rat liver folate-binding protein glycine N-methyltransferase. J. Biol. Chem [print-electronic]. 2007 Feb 2/9/2007; 282(6): 4069-75. PMID: 17158459, PII: M610384200, DOI: 10.1074/jbc.M610384200, ISSN: 0021-9258.
Loukachevitch LV, Egli M. Crystallization and preliminary X-ray analysis of Escherichia coli RNase HI-dsRNA complexes. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun [print-electronic]. 2007 Feb 2/1/2007; 63(Pt 2): 84-8. PMID: 17277445, PMCID: PMC2330121, PII: S1744309106055461, DOI: 10.1107/S1744309106055461, ISSN: 1744-3091.
Eoff RL, Irimia A, Egli M, Guengerich FP. Sulfolobus solfataricus DNA polymerase Dpo4 is partially inhibited by "wobble" pairing between O6-methylguanine and cytosine, but accurate bypass is preferred. J. Biol. Chem [print-electronic]. 2007 Jan 1/12/2007; 282(2): 1456-67. PMID: 17105728, PII: M609661200, DOI: 10.1074/jbc.M609661200, ISSN: 0021-9258.
Pallan PS, Egli M. Selenium modification of nucleic acids: preparation of oligonucleotides with incorporated 2'-SeMe-uridine for crystallographic phasing of nucleic acid structures. Nat Protoc. 2007; 2(3): 647-51. PMID: 17406626, PII: nprot.2007.75, DOI: 10.1038/nprot.2007.75, ISSN: 1750-2799.
Pallan PS, Egli M. Selenium modification of nucleic acids: preparation of phosphoroselenoate derivatives for crystallographic phasing of nucleic acid structures. Nat Protoc. 2007; 2(3): 640-6. PMID: 17406625, PII: nprot.2007.74, DOI: 10.1038/nprot.2007.74, ISSN: 1750-2799.
Egli M, Pallan PS. Insights from crystallographic studies into the structural and pairing properties of nucleic acid analogs and chemically modified DNA and RNA oligonucleotides. Annu Rev Biophys Biomol Struct. 2007; 36: 281-305. PMID: 17288535, DOI: 10.1146/annurev.biophys.36.040306.132556, ISSN: 1056-8700.
Egli M, Lubini P, Pallan PS. The long and winding road to the structure of homo-DNA. Chem Soc Rev [print-electronic]. 2007 Jan; 36(1): 31-45. PMID: 17173143, DOI: 10.1039/b606807c, ISSN: 0306-0012.
Pallan PS, Lubini P, Bolli M, Egli M. Backbone-base inclination as a fundamental determinant of nucleic acid self- and cross-pairing. Nucleic Acids Res [print-electronic]. 2007; 35(19): 6611-24. PMID: 17905816, PMCID: PMC2095819, PII: gkm612, DOI: 10.1093/nar/gkm612, ISSN: 1362-4962.
Li F, Pallan PS, Maier MA, Rajeev KG, Mathieu SL, Kreutz C, Fan Y, Sanghvi J, Micura R, Rozners E, Manoharan M, Egli M. Crystal structure, stability and in vitro RNAi activity of oligoribonucleotides containing the ribo-difluorotoluyl nucleotide: insights into substrate requirements by the human RISC Ago2 enzyme. Nucleic Acids Res [print-electronic]. 2007; 35(19): 6424-38. PMID: 17881374, PMCID: PMC2095806, PII: gkm664, DOI: 10.1093/nar/gkm664, ISSN: 1362-4962.
Egli M, Pallan PS, Pattanayek R, Wilds CJ, Lubini P, Minasov G, Dobler M, Leumann CJ, Eschenmoser A. Crystal structure of homo-DNA and nature's choice of pentose over hexose in the genetic system. J. Am. Chem. Soc. 2006 Aug 8/23/2006; 128(33): 10847-56. PMID: 16910680, DOI: 10.1021/ja062548x, ISSN: 0002-7863.
Pallan PS, von Matt P, Wilds CJ, Altmann KH, Egli M. RNA-Binding affinities and crystal structure of oligonucleotides containing five-atom amide-based backbone structures. Biochemistry. 2006 Jul 7/4/2006; 45(26): 8048-57. PMID: 16800629, DOI: 10.1021/bi060354o, ISSN: 0006-2960.
Irimia A, Zang H, Loukachevitch LV, Eoff RL, Guengerich FP, Egli M. Calcium is a cofactor of polymerization but inhibits pyrophosphorolysis by the Sulfolobus solfataricus DNA polymerase Dpo4. Biochemistry. 2006 May 5/16/2006; 45(19): 5949-56. PMID: 16681366, DOI: 10.1021/bi052511+, ISSN: 0006-2960.
Pattanayek R, Williams DR, Pattanayek S, Xu Y, Mori T, Johnson CH, Stewart PL, Egli M. Analysis of KaiA-KaiC protein interactions in the cyano-bacterial circadian clock using hybrid structural methods. EMBO J [print-electronic]. 2006 May 5/3/2006; 25(9): 2017-28. PMID: 16628225, PMCID: PMC1456936, PII: 7601086, DOI: 10.1038/sj.emboj.7601086, ISSN: 0261-4189.
Xia J, Noronha A, Toudjarska I, Li F, Akinc A, Braich R, Frank-Kamenetsky M, Rajeev KG, Egli M, Manoharan M. Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide. ACS Chem. Biol. 2006 Apr 4/25/2006; 1(3): 176-83. PMID: 17163665, DOI: 10.1021/cb600063p, ISSN: 1554-8937.
Li F, Sarkhel S, Wilds CJ, Wawrzak Z, Prakash TP, Manoharan M, Egli M. 2'-Fluoroarabino- and arabinonucleic acid show different conformations, resulting in deviating RNA affinities and processing of their heteroduplexes with RNA by RNase H. Biochemistry. 2006 Apr 4/4/2006; 45(13): 4141-52. PMID: 16566588, PMCID: PMC2553321, DOI: 10.1021/bi052322r, ISSN: 0006-2960.
Zang H, Irimia A, Choi JY, Angel KC, Loukachevitch LV, Egli M, Guengerich FP. Efficient and high fidelity incorporation of dCTP opposite 7,8-dihydro-8-oxodeoxyguanosine by Sulfolobus solfataricus DNA polymerase Dpo4. J. Biol. Chem [print-electronic]. 2006 Jan 1/27/2006; 281(4): 2358-72. PMID: 16306039, PII: M510889200, DOI: 10.1074/jbc.M510889200, ISSN: 0021-9258.
Pallan PS, Marshall WS, Harp J, Jewett FC, Wawrzak Z, Brown BA, Rich A, Egli M. Crystal structure of a luteoviral RNA pseudoknot and model for a minimal ribosomal frameshifting motif. Biochemistry. 2005 Aug 8/30/2005; 44(34): 11315-22. PMID: 16114868, PMCID: PMC2556298, DOI: 10.1021/bi051061i, ISSN: 0006-2960.
Zang H, Goodenough AK, Choi JY, Irimia A, Loukachevitch LV, Kozekov ID, Angel KC, Rizzo CJ, Egli M, Guengerich FP. DNA adduct bypass polymerization by Sulfolobus solfataricus DNA polymerase Dpo4: analysis and crystal structures of multiple base pair substitution and frameshift products with the adduct 1,N2-ethenoguanine. J. Biol. Chem [print-electronic]. 2005 Aug 8/19/2005; 280(33): 29750-64. PMID: 15965231, PII: M504756200, DOI: 10.1074/jbc.M504756200, ISSN: 0021-9258.
Egli M, Minasov G, Tereshko V, Pallan PS, Teplova M, Inamati GB, Lesnik EA, Owens SR, Ross BS, Prakash TP, Manoharan M. Probing the influence of stereoelectronic effects on the biophysical properties of oligonucleotides: comprehensive analysis of the RNA affinity, nuclease resistance, and crystal structure of ten 2'-O-ribonucleic acid modifications. Biochemistry. 2005 Jun 6/28/2005; 44(25): 9045-57. PMID: 15966728, DOI: 10.1021/bi050574m, ISSN: 0006-2960.
Diop-Frimpong B, Prakash TP, Rajeev KG, Manoharan M, Egli M. Stabilizing contributions of sulfur-modified nucleotides: crystal structure of a DNA duplex with 2'-O-[2-(methoxy)ethyl]-2-thiothymidines. Nucleic Acids Res [electronic-print]. 2005; 33(16): 5297-307. PMID: 16170156, PMCID: PMC1216336, PII: 33/16/5297, DOI: 10.1093/nar/gki823, ISSN: 1362-4962.
Haeberli P, Berger I, Pallan PS, Egli M. Syntheses of 4'-thioribonucleosides and thermodynamic stability and crystal structure of RNA oligomers with incorporated 4'-thiocytosine. Nucleic Acids Res [electronic-print]. 2005; 33(13): 3965-75. PMID: 16027443, PMCID: PMC1178003, PII: 33/13/3965, DOI: 10.1093/nar/gki704, ISSN: 1362-4962.
Egli M. Nucleic acid crystallography: current progress. Curr Opin Chem Biol. 2004 Dec; 8(6): 580-91. PMID: 15556400, PII: S1367-5931(04)00128-0, DOI: 10.1016/j.cbpa.2004.09.004, ISSN: 1367-5931.
Pattanayek R, Sethaphong L, Pan C, Prhavc M, Prakash TP, Manoharan M, Egli M. Structural rationalization of a large difference in RNA affinity despite a small difference in chemistry between two 2'-O-modified nucleic acid analogues. J. Am. Chem. Soc. 2004 Nov 11/24/2004; 126(46): 15006-7. PMID: 15547979, DOI: 10.1021/ja044637k, ISSN: 0002-7863.
Xu Y, Mori T, Pattanayek R, Pattanayek S, Egli M, Johnson CH. Identification of key phosphorylation sites in the circadian clock protein KaiC by crystallographic and mutagenetic analyses. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2004 Sep 9/21/2004; 101(38): 13933-8. PMID: 15347809, PMCID: PMC518856, PII: 0404768101, DOI: 10.1073/pnas.0404768101, ISSN: 0027-8424.
Pattanayek R, Wang J, Mori T, Xu Y, Johnson CH, Egli M. Visualizing a circadian clock protein: crystal structure of KaiC and functional insights. Mol. Cell. 2004 Aug 8/13/2004; 15(3): 375-88. PMID: 15304218, PII: S1097276504004356, DOI: 10.1016/j.molcel.2004.07.013, ISSN: 1097-2765.
Egli M. "Deoxyribo nanonucleic acid"; antiparallel, parallel, and unparalleled. Chem. Biol. 2004 Aug; 11(8): 1027-9. PMID: 15324800, PII: S107455210400211X, DOI: 10.1016/j.chembiol.2004.08.002, ISSN: 1074-5521.
Cook S, Hugli O, Egli M, Ménard B, Thalmann S, Sartori C, Perrin C, Nicod P, Thorens B, Vollenweider P, Scherrer U, Burcelin R. Partial gene deletion of endothelial nitric oxide synthase predisposes to exaggerated high-fat diet-induced insulin resistance and arterial hypertension. Diabetes. 2004 Aug; 53(8): 2067-72. PMID: 15277387, PII: 53/8/2067, ISSN: 0012-1797.
Johnson CH, Egli M. Visualizing a biological clockwork's cogs. Nature structural & molecular biology. 2004 Jul; 11(7) Sect. 584,5.
Prakash TP, Püschl A, Lesnik E, Mohan V, Tereshko V, Egli M, Manoharan M. 2'-O-[2-(guanidinium)ethyl]-modified oligonucleotides: stabilizing effect on duplex and triplex structures. Org. Lett. 2004 Jun 6/10/2004; 6(12): 1971-4. PMID: 15176796, DOI: 10.1021/ol049470e, ISSN: 1523-7060.
Egli M, Tereshko V, Mushudov GN, Sanishvili R, Liu X, Lewis FD. Face-to-face and edge-to-face pi-pi interactions in a synthetic DNA hairpin with a stilbenediether linker. J. Am. Chem. Soc. 2003 Sep 9/10/2003; 125(36): 10842-9. PMID: 12952463, DOI: 10.1021/ja0355527, ISSN: 0002-7863.
Sarkhel S, Rich A, Egli M. Water-nucleobase "stacking": H-pi and lone pair-pi interactions in the atomic resolution crystal structure of an RNA pseudoknot. J. Am. Chem. Soc. 2003 Jul 7/30/2003; 125(30): 8998-9. PMID: 15369340, DOI: 10.1021/ja0357801, ISSN: 0002-7863.
Pallan PS, Wilds CJ, Wawrzak Z, Krishnamurthy R, Eschenmoser A, Egli M. Why does TNA cross-pair more strongly with RNA than with DNA? an answer from X-ray analysis. Angew. Chem. Int. Ed. Engl. 2003; 42(47): 5893-5. PMID: 14673929, DOI: 10.1002/anie.200352553, ISSN: 1433-7851.
Wilds CJ, Pattanayek R, Pan C, Wawrzak Z, Egli M. Selenium-assisted nucleic acid crystallography: use of phosphoroselenoates for MAD phasing of a DNA structure. J. Am. Chem. Soc. 2002 Dec 12/18/2002; 124(50): 14910-6. PMID: 12475332, PII: ja021058b, ISSN: 0002-7863.
Wilds CJ, Wawrzak Z, Krishnamurthy R, Eschenmoser A, Egli M. Crystal structure of a B-form DNA duplex containing (L)-alpha-threofuranosyl (3'-->2') nucleosides: a four-carbon sugar is easily accommodated into the backbone of DNA. J. Am. Chem. Soc. 2002 Nov 11/20/2002; 124(46): 13716-21. PMID: 12431101, PII: ja0207807, ISSN: 0002-7863.
Teplova M, Wilds CJ, Wawrzak Z, Tereshko V, Du Q, Carrasco N, Huang Z, Egli M. Covalent incorporation of selenium into oligonucleotides for X-ray crystal structure determination via MAD: proof of principle. Multiwavelength anomalous dispersion. Biochimie. 2002 Sep; 84(9): 849-58. PMID: 12458077, PII: S0300908402014402, ISSN: 0300-9084.
Egli M, Minasov G, Su L, Rich A. Metal ions and flexibility in a viral RNA pseudoknot at atomic resolution. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2002 Apr 4/2/2002; 99(7): 4302-7. PMID: 11904368, PMCID: PMC123643, PII: 062055599, DOI: 10.1073/pnas.062055599, ISSN: 0027-8424.
Egli M. DNA-cation interactions: quo vadis?. Chem. Biol. 2002 Mar; 9(3): 277-86. PMID: 11927253, PII: S1074552102001163, ISSN: 1074-5521.
Joseph B, Egli M, Koppekin A, Thompson T. Food choice in people with Prader-Willi syndrome: quantity and relative preference. Am J Ment Retard. 2002 Mar; 107(2): 128-35. PMID: 11853530, DOI: 10.1352/0895-8017(2002)107<0128:FCIPWP>2.0.CO;2, ISSN: 0895-8017.
Wilds CJ, Maier MA, Tereshko V, Manoharan M, Egli M. Direct observation of a cytosine analogue that forms five hydrogen bonds to guanosine: guanidino G-clamp. Angew. Chem. Int. Ed. Engl. 2002 Jan 1/4/2002; 41(1): 115-7. PMID: 12491456, PII: 10.1002/1521-3773(20020104)41:1<115::AID-ANIE115>3.0.CO;2-R, ISSN: 1433-7851.
Tereshko V, Teplova M, Brunzelle J, Watterson DM, Egli M. Crystal structures of the catalytic domain of human protein kinase associated with apoptosis and tumor suppression. Nat. Struct. Biol. 2001 Oct; 8(10): 899-907. PMID: 11573098, PII: nsb1001-899, DOI: 10.1038/nsb1001-899, ISSN: 1072-8368.
Wilds CJ, Minasov G, Natt F, von Matt P, Altmann KH, Egli M. Studies of a chemically modified oligodeoxynucleotide containing a 5-atom amide backbone which exhibits improved binding to RNA. Nucleosides Nucleotides Nucleic Acids. 2001 Apr; 20(4-7): 991-4. PMID: 11563161, DOI: 10.1081/NCN-100002475, ISSN: 1525-7770.
Tereshko V, Wallace ST, Usman N, Wincott FE, Egli M. X-ray crystallographic observation of "in-line" and "adjacent" conformations in a bulged self-cleaving RNA/DNA hybrid. RNA. 2001 Mar; 7(3): 405-20. PMID: 11333021, PMCID: PMC1370097, ISSN: 1355-8382.
Tereshko V, Wilds CJ, Minasov G, Prakash TP, Maier MA, Howard A, Wawrzak Z, Manoharan M, Egli M. Detection of alkali metal ions in DNA crystals using state-of-the-art X-ray diffraction experiments. Nucleic Acids Res. 2001 Mar 3/1/2001; 29(5): 1208-15. PMID: 11222771, PMCID: PMC29719, ISSN: 1362-4962.
Joseph B, Egli M, Sutcliffe JS, Thompson T. Possible dosage effect of maternally expressed genes on visual recognition memory in Prader-Willi syndrome. Am. J. Med. Genet. 2001 Jan 1/8/2001; 105(1): 71-5. PMID: 11425004, PII: 10.1002/1096-8628(20010108)105:1<71::AID-AJMG1065>3.0.CO;2-8, ISSN: 0148-7299.
Teplova M, Tereshko V, Sanishvili R, Joachimiak A, Bushueva T, Anderson WF, Egli M. The structure of the yrdC gene product from Escherichia coli reveals a new fold and suggests a role in RNA binding. Protein Sci. 2000 Dec; 9(12): 2557-66. PMID: 11206077, PMCID: PMC2144518, DOI: 10.1110/ps.9.12.2557, ISSN: 0961-8368.
Sachdev RN, Egli M, Stonecypher M, Wiley RG, Ebner FF. Enhancement of cortical plasticity by behavioral training in acetylcholine-depleted adult rats. J. Neurophysiol. 2000 Oct; 84(4): 1971-81. PMID: 11024090, ISSN: 0022-3077.
Egli M, Roper T, Feurer I, Thompson T. Architectural acoustics in residences for adults with mental retardation and its relation to perceived homelikeness. Am J Ment Retard. 1999 Jan; 104(1): 53-66. PMID: 9972834, DOI: 10.1352/0895-8017(1999)104<0053:AAIRFA>2.0.CO;2, ISSN: 0895-8017.
Egli M, Joseph B, Thompson T. Transfer of social attributions in stimulus equivalence classes by preschool children. Psychol Rep. 1997 Feb; 80(1): 3-21. PMID: 9122341, DOI: 10.2466/pr0.1997.80.1.3, ISSN: 0033-2941.