PhD defense for Kaare Bjerregaard-Andersen
Cand.scient Kaare Bjerregaard-Andersen at the Centre for Molecular Medicine (NCMM) and the Department of Biosciences, Faculty of Mathematics and Natural Sciences will defend the title of his thesis for the Ph.D. degree (philosophiae doctor): Structural and biophysical studies of the mammalian Na+ dependent Cl--HCO3-exchanger NCBE and the bacterial enzyme isatin hydrolase.
The event will take place in Auditorium 3, Kristine Bonnevie, on 30 June at 13:15.
The trial lecture entitled "Intrinsically disordered proteins and structure/function relationships - reaching into translational medicine" takes place 30 June at 9:15, Auditorium 3, Kristine Bonnevie.
During his studies, Kaare Bjerregaard-Andersen used X-ray crystallography supplemented by biophysical techniques to study the molecular structure of the sodium-coupled chloride-bicarbonate exchanger (NCBE). In addition, he elucidated the protein structural basis of catalysis of the enzyme isatin hydrolase.
A stable and controlled pH is essential to cellular function. The pH can be controlled by maintaining a buffering system for minimizing the effect of sudden pH challenges to the organism. In the human body, 2/3 of the buffering capacity is based on bicarbonate. The solute carrier 4 family (SLC4) comprises the major group of membrane proteins responsible for facilitating bicarbonate transport across the plasma membrane. However, little is known about the molecular structure of this important family of proteins. During his studies, Kaare Bjerregaard-Andersen characterized the sodium-coupled chloride-bicarbonate exchanger (NCBE), a SLC4 member predominantly found in the choroid plexus of the brain and highly involved in pH homeostasis of the cerebrospinal fluid. He determined the atomic structure of the N-terminal cytoplasmic region of the protein and identified potential novel ligands. Kaare characterized regions of intrinsically disordered protein structure in the cytoplasmic domain and recognized these regions in the super family of SLC4 bicarbonate transporters. In addition to his work on NCBE, Kaare also determined the determined the atomic structure of the metalloenzyme isatin hydrolase. Here he identified a proton wire and water channel which he showed to be catalytically involved. The structural work was supported by enzyme kinetic and biophysical studies. The structure represents the first characterized member of its class of metal dependent hydrolases. Based on the enzymatic characterization he contributed to the development of a quantification assay for isatin in human blood.
These new findings contribute to our understanding of the molecular structure and function of sodium-coupled bicarbonate transporters being composed of ordered as well as disordered structure. His work provides detailed understanding of the structural basis of catalysis by the isatin hydrolase.
More information is available here.