• Deutsch
    • English
  • English 
    • Deutsch
    • English
  • Login
Item View 
  •   Home
  • Naturwissenschaften, Mathematik und Informatik
  • Fakultät für Chemie (inkl. GAUSS)
  • Item View
  •   Home
  • Naturwissenschaften, Mathematik und Informatik
  • Fakultät für Chemie (inkl. GAUSS)
  • Item View
JavaScript is disabled for your browser. Some features of this site may not work without it.

Structure, Mechanism and Inhibition of the human Glutaminyl Cyclase

by Oliver Kupski
Doctoral thesis
Date of Examination:2016-05-12
Date of issue:2017-03-24
Advisor:Prof. Dr. Kai Tittmann
Referee:Prof. Dr. Kai Tittmann
Referee:Prof. Dr. Franc Meyer
crossref-logoPersistent Address: http://dx.doi.org/10.53846/goediss-6212

 

 

Files in this item

Name:Doktorarbeit_Oliver_Kupski.pdf
Size:11.0Mb
Format:PDF
ViewOpen

The following license files are associated with this item:


Abstract

English

The mammalian zinc-dependent enzyme glutaminyl cyclase (QC, EC 2.3.2.5) belongs to the family of transferases and plays a crucial role in hormone maturation by cyclizing irreversibly N-terminal glutamines post-translationally to pyroglutamic acid (5-oxo-L-proline, pGlu) via a deamidation reaction.  Although, the physiological function of pGlu at the N-terminus seems to be essential for generation of biologically active structures, it was reported that QC is also capable to catalyze the intramolecular cyclization of N-terminal glutamic acid precursors via a dehydration reaction, which is directly connected with pathophysiological processes, especially in amyloidogenic diseases. Moreover, recent studies have shown that QC activity is abundant in brain regions, e.g. hypothalamus, and that the enzyme is probably responsible for the modification of truncated ß-amyloid (Aß) peptide species at their N-terminus in the course of Alzheimer’s disease (AD). Thus, mammalian QC might play a crucial role in the formation of the progressive neurodegenerative disorder, especially in the initial phase, and is therefore a potential drug target candidate in the therapeutic strategy to prevent amyloidogenic plaque formation. The aim of this work is to decipher the reaction mechanism of human QC in detail and based on this work to design a selective and potent inhibitor. 
Keywords: human Glutaminyl Cyclase; Carbohydrazide function; Inhibitors; Alzheimer Disease
 

Statistik

Publish here

Browse

All of eDissFaculties & ProgramsIssue DateAuthorAdvisor & RefereeAdvisorRefereeTitlesTypeThis FacultyIssue DateAuthorAdvisor & RefereeAdvisorRefereeTitlesType

Help & Info

Publishing on eDissPDF GuideTerms of ContractFAQ

Contact Us | Impressum | Data Protection Information
Göttingen State and University Library | Göttingen University