Ira Kurtz M.D. F.C.R.P.(C)

The field of membrane protein biology has evolved to the point where if we were able to understand the structure/functional relationships of medically important ion transporters, significant advances in the medical therapy of a wide range of diseases could be achieved in the not too distant future in keeping with the fact that ~ 60% of all pharmaceuticals are designed to target human membrane proteins. The Membrane Transporter Research Center includes an outstanding group of multidisciplinary investigators who have made important contributions in the field. The human SLC4 and SLC26 transporters are of particular interest to our team because of the large number of diseases they are involved in, and the centrality to human biology that bicarbonate transporting proteins are known for. We are analyzing crystals of the mammalian SLC4 transporters, AE1 and NBCe1-A, and the prokaryotic bicarbonate transporter, SbtA. A low resolution model of AE1 using EM and 3D reconstruction has been generated. The combined proven expertise of the investigators offers a unique opportunity to make very significant progress  in solving the atomic structure of several target proteins  to make advances in drug discovery and medical care.

Lab Website

Recent and Selected Publications

Pushkin, A., Kurtz, I. (2006) SLC4 base (HCO3ˉ CO32ˉ) transporters: classification, function, structure, genetic diseases, and knockout models. Am. J. Physiol. 290: 580-599. PMID: 16461757.

Leung, K., Nielsen, I.M.B., Kurtz, I. (2007) Ab initio molecular dynamics study of carbon dioxide and bicarbonate hydration and the nucleophilic attack of hydroxide of CO2. J. Phys. Chem B. 111: 4453-4459. PMID: 17408252.

Kao, L., Sassani, P., Azimov, R., Pushkin, A., Abuladze, N., Peti-Peterdi, J., Liu, W., Newman, D., Kurtz, I.  (2008) Oligomeric structure and minimal functional unit of the electrogenic sodium bicarbonate cotransporter  NBCe1-A. J. Biol. Chem. 283: 26782-26794. PMID18658147. PMCID: PMC2546552.

Zhu Q, Azimov R, Kao L, Newman D, Liu W, Abuladze N, Pushkin A, Kurtz I.(2009) NBCe1-A transmembrane segment 1 lines the ion translocation pathway.J Biol Chem. 2009 Mar 27;284(13):8918-29. PMID: 19158093

Zhu, Q., Kao, L., Azimov, R., Newman, D., Liu, W., Pushkin, A., Abuladze, N., Kurtz, I. (2010) Topological location and structural importance of the NBCe1-A residues mutated in proximal renal tubular acidosis. J. Biol. Chem. 285:13416–13426. PMID: 20197274. PMCID: PMC2859501.

Zhu Q, Kao L, Azimov R, Abuladze N, Newman D, Pushkin A, Liu W, Chang C, Kurtz I.J Biol Chem. (2010) Structural and functional characterization of the C-terminal transmembrane region of NBCe1-A. Nov 26;285(48):37178-87.  PMID: 20837482

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