Center of Excellence of the European Union
 
Set page width to 800
Login
 
Laszlo Polgar

Group leader: Prof. Laszlo Polgar

The laboratory was established in the 1960s by Dr. László Polgár, who carried out the first mutagenesis of an enzyme by converting the serine protease, subtilisin into a cysteine enzyme by chemical method. The group has been studied the mechanisms of action of various proteases, including the retroviral enzyme HIV-1 protease, the picornaviral 3C and 2A proteases and three enzymes from the prolyl oligopeptidase family, the discovery of which is associated with the group. Members of the prolyl oligopeptidase family are important targets for drug design, as they are involved in several diseases, such as mental disorders (prolyl oligopeptidase), diabetes type 2 (dipeptidyl peptidase IV), trypanosomiasis (oligopeptidase B) and carcinoma (acylaminoacyl peptidase). The enzymes of this group cannot hydrolyze proteins or peptides containing more than about 30 amino acid residues. The first crystal structure determination of the prolyl oligopeptidase family revealed that prolyl oligopeptidase consists of a serine peptidase domain with an α/β-hydrolase fold (catalytic triad: Ser554, His680, Asp641) and a regulatory -propeller domain.



Structure and function of oligopeptidase Print E-mail
Proteases have a variety of strategies for selecting substrates in order to prevent uncontrolled protein degradation. In prolyl oligopeptidase, the narrow entrance of the propeller opposite the active site is much smaller than the diameter of an average peptide, so that the substrate cannot enter through it. We have demonstrated that the propeller has stable structure, indicating that it cannot open up and the substrate should approach the catalytic site through a tunnel between the peptidase and the propeller domains. This requires the concerted movements of the two domains. This mechanism was corroborated by X-ray crystallography.