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2cvx

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{{STRUCTURE_2cvx| PDB=2cvx | SCENE= }}
{{STRUCTURE_2cvx| PDB=2cvx | SCENE= }}
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'''Structures of Yeast Ribonucleotide Reductase I'''
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===Structures of Yeast Ribonucleotide Reductase I===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_16537479}}
==About this Structure==
==About this Structure==
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[[Category: Eukaryotic]]
[[Category: Eukaryotic]]
[[Category: Ribonucleotide reductase]]
[[Category: Ribonucleotide reductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:28:01 2008''

Revision as of 11:28, 29 July 2008

Template:STRUCTURE 2cvx

Structures of Yeast Ribonucleotide Reductase I

Template:ABSTRACT PUBMED 16537479

About this Structure

2CVX is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.

Reference

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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