Alexander Pushkin, Ph.D D.Sc

The long-term aim of my research is to develop new methods to treat human diseases based on the structural organization of disease related proteins. Towards this goal our team has recently characterized by X-ray crystallography the atomic structure of aminoacylase 3, an enzyme involved in the nephrotoxicity of numerous environmental contaminants (PNAS, 107: 2010). This data is being used to predict the structures of potent and highly specific inhibitors of this enzyme to ameliorate the nephrotoxic effects of environmental contaminants. I have also played a key role in the identification of members of the SLC4 transporter family, and have also been part of Dr. Kurtz’s team in the structural study of bicarbonate transporters using X-ray crystallography and cryoEM/ET. Our team has recently generated crystals of full-length bovine AE1 and human NBCe1-A (2 bicarbonate SLC4 transporters), and a bacterial sodium bicarbonate cotransporter (SbtA). Given the increasing success of cryoEM/ET in the structural characterization of macromolecules at mid-near atomic resolution, we are also actively pursuing this promising methodology in our structural studies. One of the most difficult steps for the cryoEM/ET technique is in protein sample preparation. I have been spearheading the labs efforts with Dr. Kurtz and Zhou and we have made great progress in optimizing the sample preparation for cryoEM/ET studies of membrane proteins.

Recent and Selected Publications

Ryazantsev, S., Abuladze, N., Newman, D., Bondar, G., Kurtz, I., and Pushkin, A. (2007) Structural characterization of dimeric murine aminoacylase III. FEBS Let. 581: 1898–1902. PMID: 17434493.

Azimov, R., Abuladze, N., Sassani, P., Newman, D., Kao, L., Liu, W., Orozco, N., Ruchala, P., Pushkin, A., Kurtz, I. (2008) G418-mediated ribosomal read-through of a nonsence mutation causing autosomal recessive proximal tubular acidosis. Am. J. Physiol. 295: F633–F641. PMID: 18614622. PMCID: PMC2653109.

Zhu, Q., Azimov, R., Kao, L., Newman, D., Liu, W., Abuladze, N., Pushkin, A., and Kurtz, I. (2009) NBCe1-A transmembrane segment 1 lines the ion translocation pathway. J. Biol. Chem. 284: 8918–8929. PMID: 19158093. PMCID: PMC2659249.

Tsirulnikov, K., Abuladze, N., Newman, D., Ryazantsev, S., Wolak, T., Magilnick, N., Koag, M.-C., Kurtz, I., and Pushkin, A. (2009) Mouse aminoacylase 3: a metalloenzyme activated by cobalt and nickel. Biochim. Biophys. Acta 1794: 1049–1057. PMID: 19362172. PMCID: PMC2735877.

Tsirulnikov, K., Abuladze, N., Koag, M.-C., Newman, D., Scholz, K., Bondar, G., Zhu, Q., Avliyakulov, N.K., Dekant, W., Faull, K., Kurtz, I., and Pushkin, A. (2010) Transport of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine, a metabolite of trichloroethylene, by mouse multidrug resistance associated protein 2 (Mrp2). Toxicol. Appl. Pharmacol. 244: 218–225. PMID: 20060011. PMCID: PMC2847015.

Hsieh, J.M., Tsirulnikov, K., Sawaya, M.R., Magilnick, N., Abuladze, N., Kurtz, I., Abramson, J., and Pushkin, A. (2010) Structures of aminoacylase 3 in complex with acetylated substrates. Proc. Nat. Acad. Sci. USA. 107: 17962-17967. PMID: 20921362.