title: Density functional theory study of the manganese-containing ribonucleotide reductase from Chlamydia trachomatis: why manganese is needed in the active complex.
abstract: The active center of Chlamydia trachomatis (Ct) ribonucleotide reductase (RNR) has been studied using B3LYP hybrid density functional theory. Class Ic Ct RNR lacks the radical-bearing tyrosine that is crucial for activity in conventional class I (subclass a and b) RNR. Instead of the Fe(III)Fe(III)Tyr(rad) active state in conventional class I, Ct RNR has Mn(IV)Fe(III) at the metal center of subunit II. Based on calculated (H(+), e(-))-binding energies for Ct R2, iron-substituted Ct R2, and R2 from Escherichia coli (Ec), an explanation is proposed for why the enzyme needs this novel metal center. Mn(IV) is shown to be an equally strong oxidant as the tyrosyl radical in Ec R2. Fe(IV), however, is a much too strong oxidant and would therefore not be possible in the active cofactor. The structure of the catalytic center of the active state, such as protonation state and position of Mn, is discussed. Ct R2 has a different ligand structure than conventional class I R2 with a fourth Glu (like MMO) instead of three Glu and one Asp. Calculations indicate that, in the presence of Tyr, Glu at this position is less flexible than Asp, whereas with Phe both Glu and Asp are equally flexible. This may be a reason why conventional class I RNR has an Asp, while Ct R2, lacking the tyrosine, has a Glu.
authors.affiliation: Department of Physics, Stockholm University, SE-106 91 Stockholm, Sweden. katarina.roos@physto.se
authors.forename: Katarina
authors.initials: K
authors.lastname: Roos
authors.forename: Per E M
authors.initials: PE
authors.lastname: Siegbahn
mesh_terms: D001224:Aspartic Acid / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002692:Chlamydia trachomatis / Q000201:enzymology*; D005973:Glutamine / Q000737:chemistry / Q000378:metabolism; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D008345:Manganese / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011522:Protons; D012264:Ribonucleotide Reductases / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011522:Protons; D005973:Glutamine; D001224:Aspartic Acid; D014443:Tyrosine; D008345:Manganese; D007501:Iron; D012264:Ribonucleotide Reductases