We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

2eud

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2eud.gif|left|200px]]
+
{{Seed}}
 +
[[Image:2eud.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2eud| PDB=2eud | SCENE= }}
{{STRUCTURE_2eud| PDB=2eud | SCENE= }}
-
'''Structures of Yeast Ribonucleotide Reductase I complexed with Ligands and Subunit Peptides'''
+
===Structures of Yeast Ribonucleotide Reductase I complexed with Ligands and Subunit Peptides===
-
==Overview==
+
<!--
-
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.
+
The line below this paragraph, {{ABSTRACT_PUBMED_16537480}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 16537480 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_16537480}}
==About this Structure==
==About this Structure==
Line 32: Line 36:
[[Category: Ribonucleotide reductase]]
[[Category: Ribonucleotide reductase]]
[[Category: Subunit assembly]]
[[Category: Subunit assembly]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:07:22 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 16:10:06 2008''

Revision as of 13:10, 29 July 2008

Image:2eud.png

Template:STRUCTURE 2eud

Structures of Yeast Ribonucleotide Reductase I complexed with Ligands and Subunit Peptides

Template:ABSTRACT PUBMED 16537480

About this Structure

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

Reference

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

Page seeded by OCA on Tue Jul 29 16:10:06 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2eud"
Personal tools