2eud

<StructureSection load='2eud' size='340' side='right' caption='[[2eud]], [[Resolution|resolution]] 2.30&Aring;' scene=''>

<table><tr><td colspan='2'>[[2eud]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EUD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2EUD FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=GCQ:GEMCITABINE+DIPHOSPHATE'>GCQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RNR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ribonucleoside-diphosphate_reductase Ribonucleoside-diphosphate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.4.1 1.17.4.1] </span></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2eud FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2eud OCA], [http://pdbe.org/2eud PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2eud RCSB], [http://www.ebi.ac.uk/pdbsum/2eud PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2eud ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/RIR1_YEAST RIR1_YEAST]] Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.<ref>PMID:11893751</ref>

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

Ribonucleotide reductase (RNR) catalyzes the conversion of nucleoside diphosphates to deoxynucleoside diphosphates. Crucial for rapidly dividing cells, RNR is a target for cancer therapy. In eukaryotes, RNR comprises a heterooligomer of alpha(2) and beta(2) subunits. Rnr1, the alpha subunit, contains regulatory and catalytic sites; Rnr2, the beta subunit (in yeast, a heterodimer of Rnr2 and Rnr4), houses the diferric-tyrosyl radical crucial for catalysis. Here, we present three x-ray structures of eukaryotic Rnr1 from Saccharomyces cerevisiae: one bound to gemcitabine diphosphate (GemdP), the active metabolite of the mechanism-based chemotherapeutic agent gemcitabine; one with an Rnr2-derived peptide, and one with an Rnr4-derived peptide. Our structures reveal that GemdP binds differently from its analogue, cytidine diphosphate; because of unusual interactions of the geminal fluorines, the ribose and base of GemdP shift substantially, and loop 2, which mediates substrate specificity, adopts different conformations when binding to GemdP and cytidine diphosphate. The Rnr2 and Rnr4 peptides, which block RNR assembly, bind differently from each other but have unique modes of binding not seen in prokaryotic RNR. The Rnr2 peptide adopts a conformation similar to that previously reported from an NMR study for a mouse Rnr2-based peptide. In yeast, the Rnr2 peptide binds at subsites consisting of residues that are highly conserved among yeast, mouse, and human Rnr1s, suggesting that the mode of Rnr1-Rnr2 binding is conserved among eukaryotes. These structures provide new insights into subunit assembly and a framework for structure-based drug design targeting RNR.

Structures of eukaryotic ribonucleotide reductase I define gemcitabine diphosphate binding and subunit assembly.,Xu H, Faber C, Uchiki T, Racca J, Dealwis C Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4028-33. Epub 2006 Mar 6. PMID:16537480<ref>PMID:16537480</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 2eud" style="background-color:#fffaf0;"></div>

*[[Ribonucleotide reductase|Ribonucleotide reductase]]

[[Category: Atcc 18824]]

[[Category: Ribonucleoside-diphosphate reductase]]

[[Category: Dealwis, C]]

[[Category: Faber, C]]

[[Category: Fairman, J W]]

[[Category: Racca, J]]

[[Category: Uchiki, T]]

[[Category: Xu, H]]

[[Category: Subunit assembly]]