Structural properties of human carbonic anhydrase IX and design of its inhibitors at Masaryk University on FindAPhD.com

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Dr J Hritz No more applications being accepted Funded PhD Project (Students Worldwide)

About the Project

Carbonic anhydrase (CA) IX is cellular surface protein that in contrast to another isoforms in healthy condition is present mostly in gastrointestinal tract. However, it is highly upregulated in the cancer cells adapting to the extracellular environment while maintaining physiological conditions inside the cancer cell. The main aim of this PhD project is to characterize structural changes of CA-IX reflecting pH changes by NMR spectroscopy. It will also involve a computational design of inhibitors of CA-IX. Finally, their binding affinity will be experimentally verified by biophysical interaction methods.

PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact Jozef Hritz ([Email Address Removed]) for an informal discussion.

Information about the laboratory at: https://www.ceitec.eu/protein-structure-and-dynamics-lukas-zidek/rg110.

More information about CEITEC PhD School are available at http://ls-phd.ceitec.cz/.

References

1) Pastorekova S, Parkkila S, Parkkila AK, et al. Carbonic anhydrase IX, MN/CA IX: Analysis of stomach complementary DNA sequence and expression in human and rat alimentary tracts. Gastroenterology 1997; 112: 398-408
2) Supuran CT; Scozzafava A. (2000) Carbonic anhydrase inhibitors and their therapeutic potential. Expert Opinion on Therapeutic Patents. 10 (5): 575–600
3) Alterio, V., Di Fiore, A., De Simone, G. (2009) Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX Proc Natl Acad Sci U S A 106: 16233-16238
4) Zapletal, V.; Mládek, A.; Melková, K.; Louša, P.; Nomilner, E.; Jaseňáková, Z.; Kubáň, V.; Makovická, M.; Laníková, A.; Žídek L.; Hritz, J. Choice of force field for proteins containing structured and intrinsically disordered regions. Biophys. J. 2020, 118, 1621 – 1633
5) Nagy, G.; Oostenbrink, C.; Hritz, J. (2017) Exploring the Binding Pathways of the 14-3-3z Protein: Structural and Free-Energy Profiles Revealed by Hamiltonian Replica Exchange Molecular Dynamics with Distance Field Distance Restraints. PLoS ONE,12(7), e0180633

Structural properties of human carbonic anhydrase IX and design of its inhibitors

Masaryk University CEITEC

This project is no longer listed on FindAPhD.com and may not be available.

About the Project

References

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