Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-4-30
pubmed:abstractText
The reduction of purine nucleoside diphosphates by murine ribonucleotide reductase requires catalytic (R1) and free radical-containing (R2) enzyme subunits and deoxynucleoside triphosphate allosteric effectors. A quantitative 16 species model is presented, in which all pertinent equilibrium constants are evaluated, that accounts for the effects of the purine substrates ADP and GDP, the deoxynucleoside triphosphate allosteric effectors dGTP and dTTP, and the dimeric murine R2 subunit on both the quaternary structure of murine R1 subunit and the dependence of holoenzyme (R1(2)R2(2)) activity on substrate and effector concentrations. R1, monomeric in the absence of ligands, dimerizes in the presence of substrate, effectors, or R2(2) because each of these ligands binds R1(2) with higher affinity than R1 monomer. This leads to apparent positive heterotropic cooperativity between substrate and allosteric effector binding that is not observed when binding to the dimeric protein itself is evaluated. Allosteric activation results from an increase in k(cat) for substrate reduction upon binding of the correct effector, rather than from heterotropic cooperativity between effector and substrate. Neither the allosteric site nor the active site displays nucleotide base specificity: dissociation constants for dGTP and dTTP are nearly equivalent and K(m) and k(cat) values for both ADP and GDP are similar. R2(2) binding to R1(2) shows negative heterotropic cooperativity vis-à-vis effectors but positive heterotropic cooperativity vis-à-vis substrates. Binding of allosteric effectors to the holoenzyme shows homotropic cooperativity, suggestive of a conformational change induced by activator binding. This is consistent with kinetic results indicating full dimer activation upon binding a single equivalent of effector per R1(2)R2(2).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1651-61
pubmed:dateRevised
2010-10-4
pubmed:meshHeading
pubmed-meshheading:11327824-Allosteric Regulation, pubmed-meshheading:11327824-Animals, pubmed-meshheading:11327824-Binding Sites, pubmed-meshheading:11327824-Centrifugation, pubmed-meshheading:11327824-Dimerization, pubmed-meshheading:11327824-Enzyme Activation, pubmed-meshheading:11327824-Guanosine Diphosphate, pubmed-meshheading:11327824-Ligands, pubmed-meshheading:11327824-Light, pubmed-meshheading:11327824-Mice, pubmed-meshheading:11327824-Models, Chemical, pubmed-meshheading:11327824-Oxidation-Reduction, pubmed-meshheading:11327824-Protein Binding, pubmed-meshheading:11327824-Purine Nucleotides, pubmed-meshheading:11327824-Ribonucleoside Diphosphate Reductase, pubmed-meshheading:11327824-Ribonucleotide Reductases, pubmed-meshheading:11327824-Scattering, Radiation, pubmed-meshheading:11327824-Substrate Specificity
pubmed:year
2001
pubmed:articleTitle
A quantitative model for allosteric control of purine reduction by murine ribonucleotide reductase.
pubmed:affiliation
Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.