Alexander Mankin
Professor
Biotechnology track coordinator

 
 
Center for Pharmaceutical Biotechnology - m/c 870, University of Illinois
900 S. Ashland Ave., Chicago, IL 60607
Tel. (312) 413-1406; FAX. (312) 413-9303; e-mail: shura@uic.edu
 
 
 
 
 
 
 
 
  

 
 Research
 
 

The main areas of research in the laboratory are:

- Mechanisms of action of ribosome-targeted antibiotics;

- Functions of ribosomal RNA in protein synthesis.
- Interaction of the nascent peptide with the ribosome

The ribosome is an excellent antibiotic target. We are investigating mechanisms 
of antibiotic action and antibiotic resistance. A combination of biochemical and 
genetic approach is used to investigate how drugs interact with the ribosome and 
which new sites in the ribosome can be used as antibiotic targets.
 
Ribosomal RNA is the main structural and functional component of the ribosome. 
We are trying to understand how it functions in catalysis of peptide
bond formation. The major "missing link" in the theroy of RNA World is that rRNA 
isolated from modern ribosome is catalytically inactive. We are trying to "remind" 
rRNA that in pra-ribosome it could function without proteins. 

Functional interaction of rRNA with the nascent peptide in the ribosome exit tunnel maybe used
in regulation of gene expression and for facilitating protein folding and targeting. We are 
looking into molecular mechanism of ribosome-nascent peptide interactions. 
 

 
 
 
 

XXI century papers

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Yassin, A. and Mankin, A.S. (2007) Potential new antibiotic sites in the ribosome revealed by deleterious mutations in RNA of the large ribosomal subunit. J. Biol. Chem., 282, 24329-24342.

Toh, S.-M, Xiong, L., Arias, C.A., Villegas, M.V., Lolans, K., Quinn, J., Mankin, A.S. (2007) Acquisition of a natural resistance gene renders a clinical strain of methicillin-resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid. Molec. Microbiol. , 64, 1506-1514.

Leach, K.L., Swaney, S.M., Colca, J.R., McDonald, W.G., BlinnJ.R., Thomasco, L.M., Gadwood, R.C., Shinabarger, D. , Xiong, L., and Mankin, A.S. (2007) The site of action of oxazolidinone antibiotics in living bacteria and in human mitochondria. Mol. Cell, 26, 393-402.

Mankin, A.S. (2006) Antibiotic blocks mRNA path on the ribosome. Nat. Struct. Mol. Biol. 13, 858-860.

Tenson, T., Mankin, A.S. (2006) Antibiotics and the ribosome. Mol. Microbiol. 59,1664-1677.

Sherman, D., Xiong, L., Mankin, A.S., Melman, A. (2006) Synthesis and biological investigation of new 4''-malonyl tethered derivatives of erythromycin and clarithromycin. Bioorg. Med. Chem. Lett . 16, 1506-1509.

Mankin, A.S. (2005) Nascent peptide in the birth canal of the ribosome. Trends. Biochem. Sci . 31, 11-13.

Maguire, B.A., Beniaminov, A.D., Ramu, H., Mankin, A.S., Zimmermann, R.A. (2005) A protein component at the heart of an RNA machine: the importance of protein L27 for the function of the bacterial ribosome. Mol. Cell 20, 427-435.

Yassin, A., Fredrick, K., Mankin, A.S. (2005) Deleterious mutations in small subunit ribosomal RNA identify functional sites and potential targets for antibiotics. Proc. Natl. Acad. Sci. USA. 102, 16620-16625.

Polacek, N., Mankin, A.S. (2005) The ribosomal peptidyl transferase center: structure, function, evolution, inhibition. Crit. Revs. Biochem. Molec. Biol. 40, 285-311.

Beringer, M., Bruell, C., Xiong, L., Pfister, P., Bieling, P., Katunin, V.I., Mankin, A.S., Bottger, E.C., Rodnina, M.V. (2005) Essential mechanisms in the catalysis of peptide bond formation on the ribosome. J. Biol. Chem. 280, 36065-36072.

Xiong, L., Korkhin, Y., Mankin, A.S. (2005) Binding site of bridged ketolides in the Escherichia coli ribosome. Antimicrob. Agents Chemother. 49, 281-288.

Erlacher, M.D., Lang, K., Shankaran, N., Wotzel, B., Huttenhofer, A., Micura, R., Mankin, A.S., Polacek, N. (2005) Chemical engineering of the peptidyl transferase center reveals an important role of the 2'-hydroxyl group of A2451. Nucleic Acids Res. 33, 1618-1627.

Vimberg, V., Xiong, L., Bailey, M., Tenson, T., Mankin, A.S. (2004) Peptide-mediated macrolide resistance reveals possible specific interactions in the nascent peptide exit tunnel. Mol. Microbiol. 54, 376-385.

Colca, J.R., McDonald, W.G., Waldon, D.J., Thomasco, L.M., Gadwood,, R.C., Lund, E.T., Cavey, G.S., Mathews, W.R., Adams, L.D., Cecil, E.T., Pearson, J.D., Bock, J.H., Mott, J.E., Shinabarger, D.L., Xiong, L., Mankin, A.S. (2003) Crosslinking in the living cell locates the site of action of oxazolidinone antibiotics. J. Biol.Chem. 278, 21972-21979.

Polacek, N., Gomez, M.J., Ito, K. Xiong, L., Nakamura, Y., Mankin, A.S. (2003) The critical role of the universally conserved A2602 of 23S ribosomal RNA in the release of the nascent peptide during translation termination. Mol. Cell 11, 103-112.

Gaynor, M., Mankin, A.S. (2003) Macrolide antibiotics: binding site, mechanism of action, resistance. Curr. Top. Med. Chem. 3, 949-961.

Polacek, N., Swaney, S., Shinabarger, D., Mankin, A.S. (2002) SPARK-a novel method to monitor ribosomal peptidyl transferase activity. Biochemistry 41, 11602-11610.

Sander, P., Belova, L., Kidan, Y.G., Pfister, P., Mankin, A.S., Böttger, E.C. (2002) Ribosomal and non-ribosomal resistance to oxazolidinones: species-specific idiosyncrasy of ribosomal alterations. Mol. Microbiol. 46, 1295-1304.

Garza-Ramos, G., Xiong, L., Zhong, P., Mankin, A.S. (2001) Binding site of macrolide antibiotics on the ribosome: new resistance mutation identifies a specific interaction of ketolides with rRNA. J. Bacteriol. 183, 6898-6907.

Tenson, T., Mankin, A.S. (2001) Short peptides conferring resistance to macrolide antibiotics. Peptides 22, 1661-1668.

Polacek, N., Gaynor, M., Yassin, A., Mankin, A.S. (2001) Ribosomal peptidyl transferase can withstand mutations at the putative catalytic nucleotide. Nature 411, 498-501.

Xiong, L., Polacek, Sander, P., Boettger, E.C., Mankin, A.S. (2001) pKa of adenine 2451 in the ribosomal peptidyl transferase center remains elusive. RNA 7, 1365-1369.

Mankin, A.S. (2001) Ribosomal antibiotics. Mol. Biologia (Russ). 35, 509-520.

Belova, L., Tenson , T., Xiong, L., McNicholas, P.M., Mankin, A.S. (2001) A novel site of antibiotic action in the ribosome: Interaction of evernimicin with the large ribosomal subunit. Proc. Natl. Acad. Sci. USA 98, 3726-3731.

Bocchetta, M., Xiong, L., Shah, S., Mankin, A.S. (2001) Interactions between 23S rRNA and tRNA in the ribosomal E site. RNA 7, 54-63.

XX century papers

Xiong, L., Kloss, P., Douthwaite, S., Andersen, N.M., Swaney, S., Shinabarger, D.L., Mankin, A.S. (2000) Oxazolidinone resistance mutations in 23S rRNA of Escherichia coli reveal the central region of domain V as the primary site of drug action. J. Bacteriol., 182, 5325-5331.

Khaitovich, P., and Mankin, A. S. (2000) Reconstitution of the 50S subunit with in vitro-transcribed 23S rRNA: a new tool for studying peptidyl transferase. in The Ribosome: Structure, Function, Antibiotics, and Cellular Interactions (Garrett, R.A., Douthwaite, S.R., Liljas, A., Matheson, A.T., Moore, P.B. and Noller, H.F., eds). ASM Press, Washington, D.C., pp. 229-243.

Mankin, A. S. and Liebman, S.W (1999) Baby, don't stop! Nature Genet. 23, 8-10.

Kloss, P., Xiong, L., Shinabarger, D. and Mankin, A.S. (1999) Resistance mutations in 23S rRNA identify the site of action of protein synthesis inhibitor, linezolid, in the ribosomal peptidyl transferase center. J. Mol. Biol., 294, 93-101.

Chernyaeva, N. S., Murgola, E. J. and Mankin, A. S. (1999) Suppression of nonsense mutations induced by expression of an RNA complementary to a conserved segment of 23S rRNA. J. Bacteriol., 181,5257-5262.

Khaitovich, P., and Mankin, A. S. (1999) Effect of antibiotics on large ribosomal subunit assembly reveals possible function of 5S rRNA. J. Mol. Biol., 291, 1025-1034.

Tenson, T., Herrera, J. V., Kloss, P., Guarneros, G., and Mankin, A. S. (1999) Inhibition of translation and cell growth by minigene expression. J. Bacteriol. 181, 1617-1622.

Khaitovich, P., Tenson, T., Mankin, A. S. and Green, R. (1999) Peptidyl transferase activity catalyzed by protein-free 23S ribosomal RNA remains elusive. RNA 5, 605-608.

Khaitovich, P., Tenson, T., Kloss, P. and Mankin, A. S. (1999) Reconstitution of functionally active Thermus aquaticus large ribosomal subunits with in vitro-transcribed rRNA. Biochemistry 38, 1780-1788.

Khaitovich, P, Mankin, A. S., Green, R., Lancaster, L. and Noller, H. F. (1999) Characterization of functionally active subribosomal particles from Thermus aquaticus. Proc. Natl. Acad. Sci. USA 96, 85-90.

Xiong, L., Shah, S., Mauvais, P. and Mankin, A. S. (1999) A ketolide resistance mutation in domain II of 23S rRNA reveals proximity of hairpin 35 to the peptidyl transferase center. Mol. Microbiol. 31, 633-639.