2CVU

Structures of Yeast Ribonucleotide Reductase I

Summary for 2CVU

• Entry DOI: 10.2210/pdb2cvu/pdb
• Related: 1ZYZ 2CVS 2CVT 2CVV 2CVW 2CVX 2CVY
• Descriptor: Ribonucleoside-diphosphate reductase large chain 1, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• Functional Keywords: eukaryotic, ribonucleotide reductase, dntp regulation, oxidoreductase
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Cellular location: Cytoplasm: P21524
• Total number of polymer chains: 1
• Total formula weight: 100606.66

Authors

Xu, H.,Faber, C.,Uchiki, T.,Fairman, J.W.,Racca, J.,Dealwis, C. (deposition date: 2005-06-14, release date: 2006-03-07, Last modification date: 2024-04-03)

Primary citation

Xu, H.,Faber, C.,Uchiki, T.,Fairman, J.W.,Racca, J.,Dealwis, C.
Structures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulation
Proc.Natl.Acad.Sci.Usa, 103:4022-4027, 2006

PubMed Abstract: 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.

PubMed: 16537479
DOI: 10.1073/pnas.0600443103

Experimental method

X-RAY DIFFRACTION (2.9 Å)