Determination of the structure of KDO8P synthase with the natural substrate A5P, Z-FPEP and E-FPEP
Year: 2002
Type: conference-abstract
Abstract: Ribonucleotide reductases (rnrs) catalyse the conversion of ribonucleotides to deoxyribonucleotides and is thus an interesting target for drug design.Structural studies of rnrs by xray crystallography can be of great help in understanding the mechanism.Class I enzymes consist of two homodimeric proteins, in class Ia R1 and R2 and in Ib R1E and R2F.Ribonucleotide reductases are allosterically regulated enzymes and interact with both positive and negative effector molecules.In the class Ia enzymes two allosteric sites distinct from the active site are located in the large subunit R1.One of them, the overall activity site determines if the enzyme is active or not and apart from this a second site, the specificity site, is found.The specificity site ensures balanced dNTP pools by regulating which ribonucleotide is to be reduced.This regulation is thought to be performed through conformational changes in the large subunit.The structure of the large subunit, class Ib RNR from Salmonella typhimurium, R1E has been solved in complex with two different specificity effectors, an ATP derivate AMP-PNP and dATP.The structure reveals a similar structure to the R1 from E.coli and the most striking difference is that the overall activity site is absent in R1E.The two effectors bound to R1E show somewhat different interactions with the enzyme.Together the two structures give insight to how the regulation of the specificity of RNR class Ib is performed.
Authors: R. Vainer, N. Adir, E. Rabkin, V. Belakhov, T. Baasov
Institution: Swedish University of Agricultural Sciences
Language: English
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Open Access status: bronze
OpenAlex ID: W2032581342