Public Health Research Institute Center
UMDNJ - New Jersey Medical School
225 Warren Street
Newark, New Jersey 07103

Phone: (973) 854-3442
e-mail: mustaear@umdnj.edu



Research Summary

The research activity in Dr. Mustaev’s laboratory is focused on the development of chemical and physico-chemical approaches for studies of proteins, nucleic acids and their complexes. The object of long-term studies in the laboratory is bacterial RNA polymerase (RNAP). The main goal is understanding of the catalytic mechanism and regulation of RNA synthesis by RNAP at a molecular level of resolution.

New projects in the laboratory include: 1) drug discovery, aimed at finding a new inhibitors of bacterial transcription as potential drugs against microbial pathogens using high throughput screening (HTS). Resent activity in this direction was focused of development of fluorescence-based HTS-compatible assay for E.coli RNAP and adaptation of this assay for the enzyme from M. tuberculosis in collaboration with Dr. R. Ebright (Rutgers University). 2) Investigation of the mechanism of antibacterial and anti-cancer activity of isothiocyanates (ITC) – defense compounds of plants. This included the synthesis of highly active ITC derivatives and elucidation of their cellular targets. Collaborators: Drs. N. Kurepina and B. Kreiswirth (PHRI Center, UMDNJ). 3) Studies of the inhibitory mechanism of fluoroquinolones on bacterial topoisomerases in collaboration with Dr. K. Drlica (PHRI Center, UMDNJ). 4) Development of highly sensitive luminescent compounds as reporter groups for biological studies in collaboration with Drs. S. Marras, S. Tyagi (PHRI Center, UMDNJ), and L. Krasnoperov (NJIT). 5) Development of new probes for tomographic diagnostics of fungal and yeast infections in collaboration with Dr. D. Perlin (PHRI Center, UMDNJ).




Selected Publications


Mustaev A, Marras S. (2008) Dual-sensitizer containing luminescent compounds, conjugates and uses thereof. US patent. Publication # WO 2008/019403 A1.

Feklistov A, Mekler V, Jiang Q, Westblade L, Irschik H, Jansen R, Mustaev A,.Darst S and Ebright R. (2008) Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center. PNAS 105:14820-12825.

Kulbachinskiy A, Mustaev A.( 2006 ) Region 3.2 of the sigma subunit contributes to the binding of the 3'-initiating nucleotide in the RNA polymerase active center and facilitates promoter clearance during initiation. J Biol Chem. 281, 18273-6.

Sosunov V, Morozov S, Sosunova E, Bass I, Nikolaev A, Goldfarb A, Nikiforov V, Severinov K, Mustaev A. (2005) Involvement of the aspartate triad of the active center in all RNA polymerase catalytic activities. Nucleic Acids Res. 33, 4202-11.

Kozlov M, Bergendahl V, Burgess R, Goldfarb A, Mustaev A. (2005 ) Homogeneous fluorescent assay for RNA polymerase. Anal Biochem. Jun 9; [Epub ahead of print].

Mustaev A, Zaychikov E, Grachev M, Kozlov M, Severinov K, Epshtein V Korzheva N, Bereshchenko O, Markovtsov V, Lukhtanov E, Tsarev I, Maximova T, Kashlev M, Bass I, Nikiforov V, Goldfarb A. (2003) Strategies and methods of cross-linking of RNA polymerase active center. Methods Enzymol. 371, 191-206.

Sosunova E, Sosunov V, Kozlov M, Nikiforov V, Goldfarb A, Mustaev A. (2003) Donation of catalytic residues to RNA polymerase active center by transcription factor Gre. Proc Natl Acad Sci U S A 100, 15469-15474.

Epshtein V, Mustaev A, Markovtsov V, Bereshchenko O, Nikiforov V, Goldfarb A. (2002) Swing-gate model of nucleotide entry into the RNA polymerase active center. Mol Cell. 10, 623-634.

Korzheva N, Mustaev A. (2001) Transcription elongation complex: structure and function. Review Current Opinion in Microbiology. 4, 119-125.

Campbell EA, Korzheva N, Mustaev A, Murakami K, Goldfarb A, Darst SA (2001) Structural mechanism for rifampicin inhibition of bacterial RNA polymerase. Cell 104, 901-912.

Nudler E, Mustaev A, Lukhtanov E, Goldfarb A. (1997) The RNA-DNA hybrid maintains the register of transcription by preventing backtracking of RNA polymerase. Cell. 89,33-41.

Mustaev A, Kozlov M, Dennisova L, Zaychikov E, Markovtsov V, Goldfarb A. (1997) Modular organization of the catalytic center of RNA polymerase. Proc. Natl. Acad. Sci. U. S. A ,94, 6641-6645.

Mustaev A, Godson N. (1995) Studies of the functional topography of the catalytic center of Escherichia coli primase. J.Biol.Chem. 270, 15711-15718.

Mustaev A, Zaychikov E, Severinov K, Kashlev M, Polyakov A, Nikiforov V. Goldfarb, A. (1994) Topology of RNA Polymerase Active Center Probed by Chimerical Rifampicin-Nucleotide Compounds. Proc. Natl. Acad. Sci. U.S.A., 91, 12036-12040.

Mustaev A, Zaychikov E, Severinov K, Kashlev M, Polyakov A, Nikiforov V, Goldfarb, A. (1994) Topology of RNA Polymerase Active Center Probed by Chimerical Rifampicin-Nucleotide Compounds. Proc. Natl. Acad. Sci. U.S.A., 91, 12036-12040.

Mustaev A, Kashlev M, Lee J, Polyakov A, Lebedev A, Grachev A, Goldfarb A, Nikiforov, V. (1991) Mapping of the Priming Substrate Contacts in the Active Center of Escherichia coli RNA Polymerase. J. Biol. Chem. 266, 23927-23931.

Maximova T, Mustaev, A, Zaychikov E, Lyakhov D, Tunitskaya V, Akbarov A, Luchin S, Rechinsky V. (1991) Lys631 residue in the active site of the bacteriophage T7 RNA polymerase. Affinity labeling and site-directed mutagenesis. Eur. J. Biochem. 195, 841-842.

Morozova O. V, Mustaev A, Belyavskaya N, Zaychikov E, Kvetkova E, Wolf Yu, Pletnev A. (1990) Mapping of the region of the tick-borne encephalitis virus replicase adjacent to initiating substrate binding center. FEBS Lett. 277, 75-77.

Riva M, Carles C, Sentenac A, Grachev M, Mustaev, A, Zaychikov E. (1990) Mapping the active site of yeast RNA polymerase B (II), J. Biol. Chem. 265,16498-16503.

Zaychikov E, Mustaev, A, Glaser S, Thomm M, Grachev M, Hartmann G. (1990) Localization of a region on subunit beta' neighboring the active center of RNA polymerase from Methanobacterium thermoautotrophicum strain W. System. Appl. Microbiol. 13, 248-254.

Grachev M, Mustaev A, Zaychikov E, Lindner A, Hartmann G. (1989) Localization of the binding site for the initiating substrate on the RNA polymerase from Sulfolobus acidocaldarius. FEBS Lett. 250, 317-322.

Grachev M, Lukhtanov E, Mustaev A, Zaychikov E, Abdukayumov M, Rabinov I, Richter V, Skoblov Yu, Chistyakov P. (1989) Studies of the functional topography of Escherichia coli RNA polymerase. A method for localization of the sites of affinity labeling. Eur. J. Biochem. 180, 577-585.

Riva M, Schaeffner A, Sentenac A, Hartmann G, Mustaev A, Zaychikov E, Grachev M. (1987) Active site labeling of the RNA polymerases A, B, and C from yeast. J. Biol. Chem. 262,14377-14380.

Grachev M, Kolocheva,T, Lukhtanov E, Mustaev A. (1987) Studies on the functional topography of Escherichia coli RNA polymerase. Eur. J. Biochem. 163, 113-121.

Riva M, Schaeffner A, Sentenac A, Hartmann G, Mustaev A, Zaychikov E, Grachev M. (1987) Active site labeling of the RNA polymerases A, B, and C from yeast. J. Biol. Chem. 262,14377-14380.






Book Chapters


Mustaev A, Goldfarb A. (2004) RNA polymerase reaction in bacteria. Encyclopedia of Biological Chemistry. Elsevier Inc. 775-780.

Korzheva N. and Mustaev A. (2004). RNA and DNA polymerases as Molecular Motors. In: Molecular Motors. Schliwa M. ed. Munchen, 2002.

Grachev M, Mustaev A, Zaychikov E. (1997) Highly Selective Affinity Labeling of RNA Polymerases: A Way to Study Functional Topography of the Active Site. In: “Chemical modification of enzymes. (B.I. Kurganov, N.K.Nagradova and O.I.Lavrik eds.) Nova Science Publishers, Inc. New York 309-346.






Patents Held


Method of producing enzyme photographic material and method of producing images on it. Russian patent # SU1191874, issued 1985-11-15. BEREZIN ILYA V (SU); GRACHEV MIKHAIL A (SU); DOBRIKOV MIKHAIL I (SU); KAZANSKAYA NOVELLA F (SU); KAREL MARTINEK (SU); MUSTAEV ARKADIJ A (SU); SHISHKIN GENNADIJ V (SU).

Method for p-chlorophenyl esters of N’-O-diacyldeoxynucleotides production. Russian patent # SU1565003, issued 1994-01-30, TSVETKOV I V (RU); KOMAROVA N I (RU); LUKHTANOV E A (RU); MUSTAEV A A (RU); STAROSTIN V P (RU).

Novel isothiocyanate compounds, pharmaceutical compositions, and uses thereof. MUSTAEV A, KUREPINA N. US patent. Ref.#07763-071P01. Provisional application 2007.

Dual-sensitizer-containing luminescent compounds, conjugates and uses thereof. MUSTAEV A, MARRAS S. US patent. Ref.#07763-072P02. Provisional application 2006.






Research Funding


R01-GM30717-21 (PI Mustaev) Structure and function of RNA polymerase in E. coli. (1983-2012).

UMDNJ Collaborative Grant Award (2009-2010).

Global TB Alliance Grant Award (2009).