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Scientific Overview Research Interest Summary Principal Investigators    Yuri Bushkin, Ph.D.
   Theresa Chang, Ph.D.
   Neeraj Chauhan, Ph.D.
   Véronique Dartois, Ph.D.
   Karl Drlica, Ph.D.
   David Dubnau, Ph.D.
   Eliseo A. Eugenin, Ph.D.
   Marila Gennaro, M.D.
   Gilla Kaplan, Ph.D.
   Fred Kramer, Ph.D.
   Barry Kreiswirth, Ph.D.
   Min Lu, Ph.D.
   Leonard Mindich, Ph.D.
   Arkady Mustaev, Ph.D.
   Jyothi Nagajyothi, Ph.D.
   David Perlin, Ph.D.
   Richard Pine, Ph.D.
   Abraham Pinter, Ph.D.
   Marcela Rodriguez, Ph.D.
   Selvakumar Subbian, Ph.D.
   Sanjay Tyagi, Ph.D.
   Christopher Vinnard, M.D.
   Chaoyang Xue, Ph.D.
   Xilin Zhao, Ph.D.

   Research Faculty
   Liang Chen, Ph.D.
   Eugenie Dubnau, Ph.D.
   Jeanette Hahn, Ph.D.
   Salvatore Marras, Ph.D.
   Lanbo Shi, Ph.D.
   Yanan Zhao, Ph.D.

Emeritus Faculty Recent Publications
Arkady Mustaev, Ph.D.

Research Summary  |   Selected Publications  |   Patents Held  |  

Public Health Research Institute Center
New Jersey Medical School - Rutgers, The State University of New Jersey
225 Warren Street
Newark, New Jersey 07103

Phone: (973) 854-3442
e-mail: mustaear@njms.rutgers.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, Rutgers). 3) Studies of the inhibitory mechanism of fluoroquinolones on bacterial topoisomerases in collaboration with Dr. K. Drlica (PHRI Center, Rutgers). 4) Development of highly sensitive luminescent compounds as reporter groups for biological studies in collaboration with Drs. S. Marras, S. Tyagi (PHRI Center, Rutgers), 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, Rutgers).

Selected Publications

Bick MJ, Malik S, Mustaev A, Darst SA (2015) TFIIB is only approximately 9 A away from the 5'-end of a trimeric RNA primer in a functional RNA polymerase II preinitiation complex. PLoS One 10: e0119007. PMI: 25774659

Bae B, Nayak D, Ray A, Mustaev A, Landick R, Darst SA (2015) CBR antimicrobials inhibit RNA polymerase via at least two bridge-helix cap-mediated effects on nucleotide addition. Proc Natl Acad Sci U S A 112: E4178-4187. PMI: 26195788

Drlica K, Mustaev A, Towle TR, Luan G, Kerns RJ, Berger JM (2014) Bypassing Fluoroquinolone Resistance with Quinazolinediones: Studies of Drug-Gyrase-DNA Complexes Having Implications for Drug Design. ACS Chem Biol. PMI: 25310082

Mekler V, Minakhin L, Borukhov S, Mustaev A, Severinov K (2014) Coupling of downstream RNA polymerase-promoter interactions with formation of catalytically competent transcription initiation complex. J Mol Biol. PMI: 25311862

Mustaev A, Malik M, Zhao X, Kurepina N, Luan G, Oppegard LM, Hiasa H, Marks KR, Kerns RJ, Berger JM, Drlica K (2014) Fluoroquinolone-gyrase-DNA complexes: two modes of drug binding. J Biol Chem 289: 12300-12312. PMI: 24497635

Wirpsza L, Krasnoperov L, Mustaev A (2013) New quinolone-based thiol-reactive lanthanide luminescent probes. J Photochem Photobiol A Chem 251: 30-37. PMI: 23833545

Sosunova E, Sosunov V, Epshtein V, Nikiforov V, Mustaev A (2013) Control of transcriptional fidelity by active center tuning as derived from RNA polymerase endonuclease reaction. J Biol Chem 288: 6688-6703. PMI: 23283976

Pratt A, Garcia-Effron G, Zhao Y, Park S, Mustaev A, Pillai S, Perlin DS (2013) Evaluation of fungal-specific fluorescent labeled echinocandin probes as diagnostic adjuncts. Med Mycol 51: 103-107. PMI: 22587729

Pillai S, Krasnoperov L, Mustaev A (2013) Simple no-chromatography procedure for amine-reactive Eu luminescent chelates optimal for bioconjugation. J Photochem Photobiol A Chem 255: 16-23. PMI: 23833546

Kurepina N, Kreiswirth BN, Mustaev A (2013) Growth-inhibitory activity of natural and synthetic isothiocyanates against representative human microbial pathogens. J Appl Microbiol. PMI: 23789822

Kozlov M, Nudler E, Nikiforov V, Mustaev A (2013) Reactive rifampicin derivative able to damage transcription complex. Bioconjug Chem 24: 443-447. PMI: 23425196

Wirpsza L, Pillai S, Batish M, Marras S, Krasnoperov L, Mustaev A (2012) Highly bright avidin-based affinity probes carrying multiple lanthanide chelates. J Photochem Photobiol B 116: 22-29. PMI: 23018156

Pilllai S, Kozlov M, Marras SAE, Krasnoperov LN, Mustaev A (2012) The synthesis and characterization of new cross-linkable quinolone and quinoline-based luminescent lanthanide chelates. Progresses in Nanotechnology and Nanomaterials 1: 18-24. PMI:

Pillai S, Kozlov M, Marras SA, Krasnoperov LN, Mustaev A (2012) New cross-linking quinoline and quinolone derivatives for sensitive fluorescent labeling. J Fluoresc 22: 1021-1032. PMI: 22450725

Marks KR, Malik M, Mustaev A, Hiasa H, Drlica K, Kerns RJ (2011) Synthesis and evaluation of 1-cyclopropyl-2-thioalkyl-8-methoxy fluoroquinolones. Bioorg Med Chem Lett 21: 4585-4588. PMI: 21705218

Malik M, Marks KR, Mustaev A, Zhao X, Chavda K, Kerns RJ, Drlica K (2011) Fluoroquinolone and quinazolinedione activities against wild-type and gyrase mutant strains of Mycobacterium smegmatis. Antimicrob Agents Chemother 55: 2335-2343. PMI: 21383100

Krasnoperov LN, Marras SA, Kozlov M, Wirpsza L, Mustaev A (2010) Luminescent probes for ultrasensitive detection of nucleic acids. Bioconjug Chem 21: 319-327. PMI: 20085336

Sologub M, Litonin D, Anikin M, Mustaev A, Temiakov D (2009) TFB2 is a transient component of the catalytic site of the human mitochondrial RNA polymerase. Cell 139: 934-944. PMI: 19945377

Drlica K, Hiasa H, Kerns R, Malik M, Mustaev A, Zhao X (2009) Quinolones: action and resistance updated. Curr Top Med Chem 9: 981-998. PMI: 19747119

Feklistov A, Mekler V, Jiang Q, Westblade LF, Irschik H, Jansen R, Mustaev A, Darst SA, Ebright RH (2008) Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center. Proc Natl Acad Sci U S A 105: 14820-14825. PMI: 18787125

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: 18273-18276. PMI: 16690607

Sosunov V, Zorov S, Sosunova E, Nikolaev A, Zakeyeva I, Bass I, Goldfarb A, Nikiforov V, Severinov K, Mustaev A (2005) The involvement of the aspartate triad of the active center in all catalytic activities of multisubunit RNA polymerase. Nucleic Acids Res 33: 4202-4211. PMI: 16049026

Kozlov M, Bergendahl V, Burgess R, Goldfarb A, Mustaev A (2005) Homogeneous fluorescent assay for RNA polymerase. Anal Biochem 342: 206-213. PMI: 15950166

Mustaev A, Goldfarb A (2004), Encyclopedia of Biological Chemistry. Elsevier Inc., pp. 775-780.

Korzheva N, Mustaev A (2004) In Schliwa M (ed.), Molecular Motors, Munchen, pp. 2002.

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. PMI: 14668436

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. PMI: 14712701

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. PMI: 12408829

Korzheva N, Mustaev A (2001) Transcription elongation complex: structure and function. Curr Opin Microbiol 4: 119-125. PMI: 11282465

Campbell EA, Korzheva N, Mustaev A, Murakami K, Nair S, Goldfarb A, Darst SA (2001) Structural mechanism for rifampicin inhibition of bacterial rna polymerase. Cell 104: 901-912. PMI: 11290327

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. PMI: 9094712

Mustaev A, Kozlov M, Markovtsov V, Zaychikov E, Denissova L, Goldfarb A (1997) Modular organization of the catalytic center of RNA polymerase. Proc Natl Acad Sci U S A 94: 6641-6645. PMI: 9192618

Grachev M, Mustaev A, Zaychikov E (1997) In Kurganov BI, Nagradova NK, and Lavrik OI (eds.), Chemical modification of enzymes. Nova Science Publishers, New York, pp. 309-346.

Mustaev AA, Godson GN (1995) Studies of the functional topography of the catalytic center of Escherichia coli primase. J Biol Chem 270: 15711-15718. PMI: 7541046

Mustaev A, Zaychikov E, Severinov K, Kashlev M, Polyakov A, Nikiforov V, Goldfarb A (1994) Topology of the RNA polymerase active center probed by chimeric rifampicin-nucleotide compounds. Proc Natl Acad Sci U S A 91: 12036-12040. PMI: 7991580

Mustaev A, Kashlev M, Zaychikov E, Grachev M, Goldfarb A (1993) Active center rearrangement in RNA polymerase initiation complex. J Biol Chem 268: 19185-19187. PMI: 7690028

Mustaev A, Kashlev M, Lee JY, Polyakov A, Lebedev A, Zalenskaya K, Grachev M, 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. PMI: 1748665

Morozova OV, Belyavskaya NA, Zaychikov EF, Kvetkova EA, Mustaev AA, Pletnev AG (1991) Identification of RNA replicase subunits responsible for initiation of RNA synthesis of tick-borne encephalitis virus by affinity labelling. Biomed Sci 2: 183-186. PMI: 1772972

Riva M, Carles C, Sentenac A, Grachev MA, Mustaev AA, Zaychikov EF (1990) Mapping the active site of yeast RNA polymerase B (II). J Biol Chem 265: 16498-16503. PMI: 2204624

Grachev MA, Mustaev AA, Zaychikov EF, Lindner AJ, Hartmann GR (1989) Localisation of the binding site for the initiating substrate on the RNA polymerase from Sulfolobus acidocaldarius. FEBS Lett 250: 317-322. PMI: 2502428

Grachev MA, Lukhtanov EA, Mustaev AA, Zaychikov EF, Abdukayumov MN, Rabinov IV, Richter VI, Skoblov YS, Chistyakov PG (1989) Studies of the functional topography of Escherichia coli RNA polymerase. A method for localization of the sites of affinity labelling. Eur J Biochem 180: 577-585. PMI: 2496979

Riva M, Schaffner AR, Sentenac A, Hartmann GR, Mustaev AA, Zaychikov EF, Grachev MA (1987) Active site labeling of the RNA polymerases A, B, and C from yeast. J Biol Chem 262: 14377-14380. PMI: 3667579

Grachev MA, Kolocheva TI, Lukhtanov EA, Mustaev AA (1987) Studies on the functional topography of Escherichia coli RNA polymerase. Highly selective affinity labelling by analogues of initiating substrates. Eur J Biochem 163: 113-121. PMI: 3545823

Patents Held

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

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.

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