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dc.contributorWichita State University. Department of Chemistryen_US
dc.contributor.authorWimalasena, Kandategeen_US
dc.contributor.authorDharmasena, Silpadipathialageen_US
dc.contributor.authorWimalasena, D. Shyamalien_US
dc.contributor.authorHughbanks-Wheaton, Dianna K.en_US
dc.date.accessioned2012-02-06T17:17:02Z
dc.date.available2012-02-06T17:17:02Z
dc.date.issued1996-10-18en_US
dc.identifier8824243en_US
dc.identifier2985121Ren_US
dc.identifierGM45026en_US
dc.identifier.citationThe Journal of biological chemistry. 1996 Oct 18; 271(42): 26032-43.en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10057/4385
dc.descriptionAccess full text below in the Files in this item section.en_US
dc.description.abstractThe interactions of reductants with dopamine beta-monooxygenase (DbetaM) were examined using two novel classes of reductants. The steady-state kinetics of the previously characterized DbetaM reductant, N,N-dimethyl-1,4-p-phenylenediamine (DMPD), were parallel to the ascorbic acid-supported reaction with respect to pH dependence and fumarate activation. DMPD also displayed pH and fumarate-dependent apparent negative cooperativity demonstrating that the previously reported cooperative behavior of DbetaM toward the reductant is not unique to ascorbic acid. The 6-OH phenyl and alkylphenyl-substituted ascorbic acid derivatives were more efficient reductants for the enzyme than ascorbic acid. Kinetic studies suggested that these derivatives behave as pseudo bisubstrates with respect to ascorbic acid and the amine substrate. The lack of apparent cooperative behavior with these derivatives suggests that this behavior of DbetaM is not common for all the reductants. Based on these findings and additional kinetic evidence, the proposal that the apparent negative cooperativity in the interaction of ascorbic acid with DbetaM was due to the presence of a distinct allosteric regulatory site has been ruled out. In contrast to previous models, where fumarate was proposed to interact with a distinct anion binding site, the effect of fumarate on the steady-state kinetics of these novel reductants suggests that fumarate and the reductant may interact with the same site of the enzyme. In accordance with these observations and mathematical analysis of the experimental data, a unified model for the apparent negative cooperativity and fumarate activation of DbetaM in which both fumarate and the reductant interact with the same site of all forms of the enzyme with varying affinities under steady-state turnover conditions has been proposed.en_US
dc.description.sponsorshipNIGMS NIH HHSen_US
dc.format.extent26032-43en_US
dc.language.isoengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen_US
dc.relation.ispartofseriesThe Journal of biological chemistryen_US
dc.relation.ispartofseriesJ. Biol. Chem.en_US
dc.sourceNLMen_US
dc.subjectResearch Support, U.S. Gov't, P.H.S.en_US
dc.subject.meshAnticarcinogenic Agents/pharmacologyen_US
dc.subject.meshChromatography, High Pressure Liquiden_US
dc.subject.meshDopamine beta-Hydroxylase/metabolismen_US
dc.subject.meshEnzyme Activationen_US
dc.subject.meshFumarates/pharmacologyen_US
dc.subject.meshHydrogen-Ion Concentrationen_US
dc.subject.meshKineticsen_US
dc.subject.meshModels, Chemicalen_US
dc.subject.meshPhenylenediamines/metabolismen_US
dc.titleReduction of dopamine beta-monooxygenase. A unified model for apparent negative cooperativity and fumarate activationen_US
dc.typeArticleen_US
dc.coverage.spacialUnited Statesen_US
dc.description.versionpeer revieweden_US
dc.rights.holderCopyright © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.en_US


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