2cvs
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Structures of Yeast Ribonucleotide Reductase I
OverviewOverview
Ribonucleotide reductase catalyzes a crucial step in de novo DNA synthesis, and is allosterically controlled by relative levels of dNTPs to maintain a, balanced pool of deoxynucleoside triphosphates in the cell. In eukaryotes, the enzyme comprises a heterooligomer of alpha(2) and beta(2) subunits., The alpha subunit, Rnr1, contains catalytic and regulatory sites. Here, we, report the only x-ray structures of the eukaryotic alpha subunit of, ribonucleotide reductase from Saccharomyces cerevisiae. The structures of, the apo-, AMPPNP only-, AMPPNP-CDP-, AMPPNP-UDP-, dGTP-ADP- and, TTP-GDP-bound complexes give insight into substrate and effector binding, and specificity cross-talk. These are Class I structures with the only, fully ordered catalytic sites, including loop 2, a stretch of polypeptide, that spans specificity and catalytic sites, conferring specificity., Binding of specificity effector rearranges loop 2; in our structures, this, rearrangement moves P294, a residue unique to eukaryotes, out of the, catalytic site, accommodating substrate binding. Substrate binding further, rearranges loop 2. Cross-talk, by which effector binding regulates, substrate preference, occurs largely through R293 and Q288 of loop 2, which are analogous to residues in Thermotoga maritima that mediate, cross-talk. However loop-2 conformations and residue-substrate, interactions differ substantially between yeast and T. maritima. In most, effector-substrate complexes, water molecules help mediate substrate-loop, 2 interactions. Finally, the substrate ribose binds with its 3' hydroxyl, closer than its 2' hydroxyl to C218 of the catalytic redox pair. We also, see a conserved water molecule at the catalytic site in all our, structures, near the ribose 2' hydroxyl.
About this StructureAbout this Structure
2CVS is a Single protein structure of sequence from Saccharomyces cerevisiae. Active as Ribonucleoside-diphosphate reductase, with EC number 1.17.4.1 Full crystallographic information is available from OCA.
ReferenceReference
Structures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulation., Xu H, Faber C, Uchiki T, Fairman JW, Racca J, Dealwis C, Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4022-7. Epub 2006 Mar 6. PMID:16537479
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