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Structural and kinetic studies of human carbonic anhydrases as multiple drug targets



Funding: European Regional Development Fund (ERDF) “On Implementation of Activity “Post-doctoral Research Aid” of the Specific Aid Objective 1.1.1 “To increase the research and innovative capacity of scientific institutions of Latvia and the ability to attract external financing, investing in human resources and infrastructure” of the Operational Programme “Growth and Employment”

Project Title: Structural and kinetic studies of human carbonic anhydrases as multiple drug targets

Project No.:

Period: 36 months (1 February 2020 – 31 January 2023)

Project costs: 133 806.00 EUR

Project implementer: Dr. biol. Jānis Leitāns


Summary of project:

Carbonic anhydrases (CAs) are widespread enzymes that catalyze the interconversion of a water molecule and carbon dioxide into bicarbonate and hydrogen ions. There are at least 16 known mammalian CA isoforms. Although most of them are responsible for important processes in the organism, some isoform enzymatic activity is associated with different diseases. Human CA IX (hCA IX) is overexpressed in many tumor types and it has been proposed that hCA IX enzymatic activity favors tumor spread. The project consists of multiple hCA IX-ligand complex structural studies and the acquisition of structural knowledge for mitochondrial CA isoforms Va and Vb. These results will notably increase the available structural data of tumor associated hCA IX and de novo structure determination of hCA Va and/or hCA Vb isoforms with further use in anti-obesity drug design. 

Information published 03.02.2020. 


Project progress

 1 February 2020 – 30 April 2020

Started the optimization of the hCA Va and hCA Vb expression, production and purification systems. hCA Va has been successfully expressed in E.coli, resulting in significant amount of enzymatically active and soluble hCA Va protein. Initial purification protocol has been developed with ongoing optimization steps.

Information published 30.04.2020.


Project progress

 1 May 2020 – 31 July 2020

Purification system of the hCA Va is being optimized and initial crystallization condition screening was started. hCA IX enzyme was co-crystallized with various sulfonamide inhibitors.

Information published 31.07.2020

Mājas lapas izstrādi finansēja ERAF aktivitātes projekts Nr. 2010/0196/2DP/ "Latvijas biomedicīnas pētījumu integrācija Eiropas zinātnes telpā".