1ZZD

Structures of Yeast Ribonucleotide Reductase I

1ZZD の概要

• エントリーDOI: 10.2210/pdb1zzd/pdb
• 分子名称: Ribonucleoside-diphosphate reductase large chain 1, Ribonucleoside-diphosphate reductase small chain 2 (3 entities in total)
• 機能のキーワード: eukaryotic, ribonucleotide reductase, dntp regulation, oxidoreductase
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast); 詳細
• 細胞内の位置: Cytoplasm: P21524; Nucleus: P49723
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 100816.16

構造登録者

Xu, H.,Faber, C.,Uchiki, T.,Fairman, J.W.,Racca, J.,Dealwis, C. (登録日: 2005-06-13, 公開日: 2006-03-07, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.6 Å)