title: The enantioselectivities of the active and allosteric sites of mammalian ribonucleotide reductase.
abstract: Here we examine the enantioselectivity of the allosteric and substrate binding sites of murine ribonucleotide reductase (mRR). L-ADP binds to the active site and L-ATP binds to both the s- and a-allosteric sites of mR1 with affinities that are only three- to 10-fold weaker than the values for the corresponding D-enantiomers. These results demonstrate the potential of L-nucleotides for interacting with and modulating the activity of mRR, a cancer chemotherapeutic and antiviral target. On the other hand, we detect no substrate activity for L-ADP and no inhibitory activity for N3-L-dUDP, demonstrating the greater stereochemical stringency at the active site with respect to catalytic activity.
authors.affiliation: Department of Chemistry, University of Pennsylvania, PA 19104-6323, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.forename: Béatrice
authors.initials: B
authors.lastname: Roy
authors.forename: Christian
authors.initials: C
authors.lastname: Périgaud
authors.forename: Ossama B
authors.initials: OB
authors.lastname: Kashlan
authors.forename: Barry S
authors.initials: BS
authors.lastname: Cooperman
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D001665:Binding Sites; D003565:Cytidine Diphosphate / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D012262:Ribonucleoside Diphosphate Reductase / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity / Q000235:genetics
chemical_list: D021122:Protein Subunits; D011994:Recombinant Proteins; D000244:Adenosine Diphosphate; D003565:Cytidine Diphosphate; D000255:Adenosine Triphosphate; C019857:CDP reductase; D012262:Ribonucleoside Diphosphate Reductase