3K8T

Structure of eukaryotic rnr large subunit R1 complexed with designed adp analog compound

Summary for 3K8T

• Entry DOI: 10.2210/pdb3k8t/pdb
• Descriptor: Ribonucleoside-diphosphate reductase large chain 1, MAGNESIUM ION, 2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: eukaryotic ribonucleotide reductase, nucleotide analogs, allosteric enzyme atp-binding, dna replication, nucleotide-binding oxidoreductase, phosphoprotein, allosteric enzyme, atp-binding, nucleotide-binding, oxidoreductase
• Biological source: Saccharomyces cerevisiae (yeast)
• Cellular location: Cytoplasm: P21524
• Total number of polymer chains: 1
• Total formula weight: 100751.82

Authors

Sun, D.,Xu, H.,Dealwis, C.,Lee, R.E. (deposition date: 2009-10-14, release date: 2010-03-02, Last modification date: 2023-09-06)

Primary citation

Sun, D.,Xu, H.,Wijerathna, S.R.,Dealwis, C.,Lee, R.E.
Structure-Based Design, Synthesis, and Evaluation of 2'-(2-Hydroxyethyl)-2'-deoxyadenosine and the 5'-Diphosphate Derivative as Ribonucleotide Reductase Inhibitors
Chemmedchem, 4:1649-1656, 2009

PubMed Abstract: Analysis of the recently solved X-ray crystal structures of Saccharomyces cerevisiae ribonucleotide reductase I (ScRnr1) in complex with effectors and substrates led to the discovery of a conserved water molecule located at the active site that interacted with the 2'-hydroxy group of the nucleoside ribose. In this study 2'-(2-hydroxyethyl)-2'-deoxyadenosine 1 and the 5'-diphosphate derivative 2 were designed and synthesized to see if the conserved water molecule could be displaced by a hydroxymethylene group, to generate novel RNR inhibitors as potential antitumor agents. Herein we report the synthesis of analogues 1 and 2, and the co-crystal structure of adenosine diphosphate analogue 2 bound to ScRnr1, which shows the conserved water molecule is displaced as hypothesized.

PubMed: 19681093
DOI: 10.1002/cmdc.200900236

Experimental method

X-RAY DIFFRACTION (2.1 Å)