Photo of Polikanov, Yury

Yury Polikanov, PhD

Assistant Professor

Biological Sciences

Contact

Building & Room:

4170 MBRB

Address:

900 S. Ashland Ave.

Office Phone Voice:

(312) 413-2408

Email:

yuryp@uic.edu

About

Mission Statement

The ultimate goal of our laboratory is to be among the most successful and respected in the field of structural biology. In particular, we are focused on studies of structural aspects of protein synthesis and the mechanisms of action of ribosome-targeting antibiotics. Our vision is that our research will facilitate the development of next-generation antimicrobial compounds, as well as clinical approaches to prevent acquisition of drug resistance by clinical pathogens. As part of our research, we wish to contribute to the fundamental understanding of how multiple elements of the ribosome function together during protein synthesis and what are their individual roles in this process at the molecular level. Also, we are focused on creating a learning environment for the training of next-generation scientists through our teamwork and through fostering scientific excellence.

 

About Dr. Polikanov's Research

Our research is focused on elucidating the structure and functions of the ribosome, understanding the basic principles of protein synthesis in bacteria, the modes of action of ribosome-targeting antibiotics, and mechanisms of drug resistance at a structural level. While the general process of protein synthesis is relatively well understood, several fundamental questions central to the ribosome structure, function and evolution remain obscure. Understanding these aspects of translation is greatly facilitated by the use of X-ray crystallography technique that provides a structural basis for the molecular mechanisms, by which the ribosome and associated translation factors (such as release factors) achieve their roles in protein synthesis. We use cutting-edge X-ray crystallography technique to determine atomic-resolution structures of the bacterial ribosome in functional complexes with various translation factors and ribosome-targeting antibiotics. Our structures provide the basis for the understanding of how different elements of ribosome function together at the molecular level. Importantly, using the functionally relevant ribosome complexes, such as those that contain natural tRNA substrates, we produce principally new data, highly relevant to the actual mechanism of action of an antibiotic or a translation factor.

Our new laboratory was established in 2015 when I joined the team of faculty at the Department of Biological Sciences jointly with the Department of Medicinal Chemistry and Pharmacognosy at the University of Illinois at Chicago (UIC). As an independent laboratory, we have already published several experimental papers, in which we have unraveled the mechanisms of action of several new antibiotics and revised the modes of action of a number of the old drugs. We found that structural models showing how various translation factors and antibiotics interact with vacant bacterial ribosomes can provide information that is incomplete or possibly even misleading, which is because the critical interactions of a factor/antibiotic and the ribosome critically depend on the presence of natural ribosomal ligands, such as mRNA and tRNAs. We started to routinely use ribosome complexes containing natural tRNAs that fortuitously led us to a significantly higher resolution of our electron density maps due to the stabilization provided by the ribosome-bound tRNA molecules. We believe that only the high-resolution structures of various translation factors bound to the functionally meaningful complexes of the ribosome can supply information essential for understanding the actual mechanisms of their action. In the course of our studies, we have generated resources and techniques, which are in high demand in other research laboratories in academia and the pharmaceutical industry.

Selected Publications

Peer-Reviewed Publications from UIC (* – corresponding author)

  1. Khabibullina NF, Tereshchenkov AG, Komarova ES, Syroegin EA, Shiriaev DI, Paleskava A, Kartsev VG, Bogdanov AA, Konevega AL, Dontsova OA, Sergiev PV, Osterman IA*, and Polikanov YS*. (2019) Structure of dirithromycin bound to the bacterial ribosome suggests new ways for rational improvement of macrolides. Antimicrobial Agents and Chemotherapy, in press.
  2. Svetlov MS, Plessa E, Chen CW, Bougas A, Krokidis MG, Dinos GP*, and Polikanov YS*. (2019) High-resolution crystal structures of ribosome-bound chloramphenicol and erythromycin provide the ultimate basis for their competition. RNA Journal, doi: 10.1261/rna.069260.118.
  3. Matsushita T, Sati G, Kondasinghe N, Pirrone M, Kato T, Waduge P, Kumar H, Sanchon A, Dobosz-Bartoszek M, Shcherbakov D, Juhas M, Hobbie SN, Schrepfer T, Chow CS, Polikanov YS, Schacht J, Vasella A, Böttger EC*, and Crich D*. (2019) Design, multigram synthesis, and in vitro and in vivo evaluation of propylamycin: a semisynthetic 4,5-deoxystreptamine class aminoglycoside for the treatment of drug-resistant Enterobacteriaceae and other Gram-negative pathogens. Journal of American Chemical Society, doi: 10.1021/jacs.9b01693.
  4. Juhas M, Widlake E, Teo J, Huseby DL, Tyrrell JM, Polikanov YS, Ercan O, Petersson A, Cao S, Aboklaish AF, Rominski A, Crich D, Böttger EC, Walsh TR, Hughes D, and Hobbie SN*. (2019) In vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii. Journal of Antimicrobial Chemotherapy 74(4): 944-952.
  5. Melnikov SV, Khabibullina NF, Mairhofer E, Vargas-Rodriguez O, Reynolds NM, Micura R*, Söll D*, and Polikanov YS*. (2018) Mechanistic insights into the slow peptide bond formation with D-amino acids in the ribosomal active site. Nucleic Acids Research 47(4): 2089-2100.
  6. Pantel L, Florin T, Dobosz-Bartoszek M, Racine E, Sarciaux M, Serri M, Houard J, Campagne JM, Marcia de Figueiredo R, Midrier C, Gaudriault S, Givaudan A, Lanois A, Forst S, Aumelas A, Cotteaux-Lautard C, Bolla JM, Vingsbo Lundberg C, Huseby DL, Hughes D, Villain-Guillot P, Mankin AS*, Polikanov YS*, and Gualtieri G*. (2018) Odilorhabdins, antibacterial agents that cause miscoding by binding at a new ribosomal site. Molecular Cell 70(1): 83-94.
  7. Lin J, Zhou D, Steitz TA*, Polikanov YS*, and Gagnon MG*. (2018) Ribosome-targeting antibiotics: Modes of action, mechanisms of resistance, and implications for drug design. Annual Review of Biochemistry 87: 451-478.
  8. Polikanov YS*, Aleksashin NA, Beckert B, and Wilson DN*. (2018) The mechanisms of action of ribosome-targeting peptide antibiotics. Frontiers in Molecular Biosciences 5: 48.
  9. Tereshchenkov AG, Dobosz-Bartoszek M, Osterman IA, Marks J, Sergeeva VA, Kasatsky P, Komarova ES, Stavrianidi AA, Rodin IA, Konevega AL, Sergiev PV, Sumbatyan NV, Mankin AS, Bogdanov AA*, and Polikanov YS*. (2018) Binding and action of amino acid analogs of chloramphenicol upon the bacterial ribosome. Journal of Molecular Biology 430(6): 842-852.
  10. Sergiev PV, Aleksashin NA, Chugunova AA, Polikanov YS*, and Dontsova OA*. (2018) Structural and evolutionary insights into ribosomal RNA methylation. Nature Chemical Biology 14(3): 226-235.
  11. Metelev M, Osterman IA, Ghilarov D, Khabibullina NF, Yakimov A, Shabalin K, Utkina I, Travin DY, Komarova ES, Serebryakova M, Artamonova T, Khodorkovskii M, Konevega AL, Sergiev PV, Severinov K*, and Polikanov YS*. (2017) Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel. Nature Chemical Biology 13(10): 1129-1136.
  12. Almutairi MM, Svetlov MS, Hansen DA, Khabibullina NF, Klepacki D, Kang HY, Sherman DH, Vázquez-Laslop N, Polikanov YS*, and Mankin AS*. (2017) Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins. Nucleic Acids Research 45(16): 9573-9582.
  13. Osterman IA, Khabibullina NF, Komarova ES, Kasatsky P, Kartsev VG, Bogdanov AA, Dontsova OA, Konevega AL*, Sergiev PV*, and Polikanov YS*. (2017) Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state. Nucleic Acids Research 45(12): 7507-7514.
  14. Karabadzhak AG, Petti LM, Barrera FN, Edwards APB, Moya-Rodríguez A, Polikanov YS, Freites JA, Tobias DJ, Engelman DM*, and DiMaio D*. (2017) Two transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF β receptor in an active dimeric conformation. Proceedings of the National Academy of Sciences USA 114(35): E7262-E7271.
  15. Arenz S, Juette MF, Graf M, Nguyen F, Huter P, Polikanov YS*, Blanchard SC*, and Wilson DN*. (2016) Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome. Proceedings of the National Academy of Sciences USA 113(27): 7527-7532.
  16. Melnikov SV, Söll D, Steitz TA*, Polikanov YS*. (2016) Insights into RNA binding by the anticancer drug cisplatin from the crystal structure of cisplatin-modified ribosome. Nucleic Acids Research 44(10): 4978-4987.

 

Peer-Reviewed Publications from Yale University

  1. Polikanov YS and Moore PB*. (2015) Acoustic vibrations contribute to the diffuse scatter produced by ribosome crystals. Acta Crystallographica Section D 71(Pt 10): 2021-2031.
  2. Polikanov YS, Starosta AL, Juette MF, Altman RB, Terry DS, Lu W, Burnett BJ, Dinos G, Reynolds K, Blanchard SC*, Steitz TA*, and Wilson DN*. (2015) Distinct tRNA accommodation intermediates observed on the ribosome with the antibiotics Hygromycin A and A201A. Molecular Cell 58(5): 832-844.
  3. Polikanov YS, Melnikov SV, Söll D*, and Steitz TA*. (2015Structural insights into the role of rRNA modifications in protein synthesis and ribosome assembly. Nature Structural & Molecular Biology 22(4): 342-344.
  4. Polikanov YS, Osterman IA, Szal T, Tashlitsky VN, Serebryakova MV, Kusochek P, Bulkley D, Malanicheva IA, Efimenko TA, Efremenkova OV, Konevega AL, Shaw KJ, Bogdanov AA, Rodnina MV, Dontsova OA, Mankin AS*, Steitz TA*, and Sergiev PV*. (2014Amicoumacin A inhibits translation by stabilizing mRNA interaction with the ribosome. Molecular Cell 56(4): 531-540.
  5. Polikanov YS, Szal T, Jiang F, Gupta P, Matsuda R, Shiozuka M, Steitz TA*, Vázquez-Laslop N*, and Mankin AS*. (2014Negamycin interferes with decoding and translocation by simultaneous interaction with rRNA and tRNA. Molecular Cell 56(4): 541-550.
  6. Polikanov YS, Steitz TA*, and Innis CA*. (2014A proton wire to couple aminoacyl-tRNA accommodation and peptide-bond formation on the ribosome. Nature Structural & Molecular Biology 21(9): 787-793. Selected for the cover image.
  7. Polikanov YS, Blaha GM, and Steitz TA*. (2012How hibernation factors RMF, HPF, and YfiA turn off protein synthesis. Science 336(6083): 915-918.
  8. Bulkley D, Brandi L,  Polikanov YS, Fabbretti A, O’Connor M, Gualerzi CO*, and Steitz TA*. (2014The antibiotics dityromycin and GE82832 bind protein S12 and block EF-G-catalyzed translocation. Cell Reports S2211-1247(13): 00782-1.
  9. Blaha GM, Polikanov YS, and Steitz TA*. (2012Elements of ribosomal drug resistance and specificity. Current Opinion in Structural Biology 22(6): 750- 758.\

 

Complete List of Peer-Reviewed Publications

https://www.ncbi.nlm.nih.gov/sites/myncbi/yury.polikanov.1/bibliography/50395623/public/?sort=date&direction=descending

 

Notable Honors

2019, UIC Rising Star Award – Researcher of the Year , UIC

2008, Achievement Award for Outstanding Thesis Research, UMDNJ/Rutgers

2004, Best Student of Lomonosov Moscow State University of Year 2004, Lomonosov Moscow State University

2004, Student Commencement Speaker, Lomonosov Moscow State University

Education

Post-Doctoral Training, Biophysics, 2008-2015 - Yale University (Advisor: Prof. Thomas A. Steitz)

PhD, Pharmacology, Magna Cum Laude, 2008 - University of Medicine and Dentistry of New Jersey jointly with Rutgers University (Advisor: Prof. Vasily M. Studitsky)

MS, Biochemistry, Cum Laude, 2004 - Lomonosov Moscow State University, Russia (Advisor: Prof. Vladimir A. Gvozdev)