| |
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
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.
|
