Licentiate thesis: The Manganese-Iron Center in Chlamydia Ribonucleotide Reductase - Insigths from Theoretical Modeling

by Katarina Roos (Stockholm University, Department of Physics)

Monday 31 May 2010, 14:00 → 16:00 Europe/Stockholm

Magnélisalen, Kemiska övningslaboratoriet

Ribonucleotide reductase (RNR) catalyzes the formation of the building blocks for DNA. Subunit II of class I RNR is a diiron protein where a stable tyrosyl radical, needed for substrate catalysis, is formed by reductive cleavage of oxygen. RNR from Chlamydia trachomatis (Ct) lacks the tyrosine, and instead the active cofactor has a Mn(IV)Fe(III) metal center. The scientific interest in the manganese-containing Chlamydia RNR is motivated for at least two reasons. 1. Biological relevance: The central role of RNRs in nucleotide metabolism makes them essential in all cellular organisms, and Ct RNR defines a completely new subclass. Chlamydia is a human pathogen, and in the light of todays increasing problem with antibiotics resistance Ct RNR could be a potential drug target. 2. Chemical relevance: A mixed MnFe metal center has never been observed as a radical cofactor before. Understanding how Ct RNR works will increase our knowledge on iron and manganese in enzymes and how they can be combined, possibly to form new catalysts. In the present thesis density functional theory (a quantum mechanical method) is used to study the MnFe center of Ct RNR. Some of the questions addressed are why Mn is needed in Ct RNR, and how different combinations of metals affect oxygen cleavage.