| pubmed-article:8241177 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:8241177 | lifeskim:mentions | umls-concept:C1167622 | lld:lifeskim |
| pubmed-article:8241177 | lifeskim:mentions | umls-concept:C0024485 | lld:lifeskim |
| pubmed-article:8241177 | lifeskim:mentions | umls-concept:C1442080 | lld:lifeskim |
| pubmed-article:8241177 | lifeskim:mentions | umls-concept:C1705822 | lld:lifeskim |
| pubmed-article:8241177 | lifeskim:mentions | umls-concept:C0007382 | lld:lifeskim |
| pubmed-article:8241177 | lifeskim:mentions | umls-concept:C0348011 | lld:lifeskim |
| pubmed-article:8241177 | lifeskim:mentions | umls-concept:C2603343 | lld:lifeskim |
| pubmed-article:8241177 | pubmed:issue | 48 | lld:pubmed |
| pubmed-article:8241177 | pubmed:dateCreated | 1994-1-6 | lld:pubmed |
| pubmed-article:8241177 | pubmed:abstractText | UDP-galactose 4-epimerase contains NAD+ irreversibly but noncovalently bound to the active site. Uridine nucleotides bind to the substrate site and induce a protein conformational change that increases the chemical reactivity of NAD+ at the coenzyme site. Activation of NAD+ by uridine nucleotides perturbs the 15N and 13C NMR chemical shifts of selectively enriched NAD+ bound to the coenzyme site. The proton-decoupled 15N NMR signal for enzyme-bound [carboxamide-15N]NAD+ does not change upon addition of UDP, indicating that activation is not brought about by a change in the binding of the carboxamide group. The 15N NMR signal of enzyme-bound [nicotinamide-1-15N]NAD+ is shifted upfield 3.0 ppm and the 13C NMR signal for [nicotinamide-4-13C]NAD+ is shifted downfield 3.4 ppm downfield by the binding of UDP at the substrate site. These changes are consistent with the induction of a distortion into the nicotinamide ring, in which positive charge is transferred from N-1 to C-4. The kinetic and thermodynamic effects of these perturbations are significant, as indicated by the nonenzymatic chemical reactivities of a series of N-alkyl nicotinamides differing in the inductive electron withdrawing effects of the alkyl substituents. A downfield change of 3.4 ppm in the 4-13C chemical shifts brought about by electron withdrawal in the model compounds corresponds to a 3200-fold increase in the rate of reduction by NaBH3CN in water, a 15,000-fold increase in 86% ethanol, and a 152 mV more positive reduction potential in this series. The distortion of NAD+ by the binding of UDP is a long-range effect that is transmitted from the substrate binding site to the coenzyme through the protein conformational change. This apparently distorts the pi-electron distribution in the nicotinamide ring and reduces the activation energy for its reduction. Activation of enzyme-bound NAD+ toward reduction apparently arises from a destabilization in the nicotinamide ring structure rather than from a stabilization of the transition state through attractive interactions between the nicotinamide ring and the enzyme. | lld:pubmed |
| pubmed-article:8241177 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:8241177 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:8241177 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:8241177 | pubmed:language | eng | lld:pubmed |
| pubmed-article:8241177 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:8241177 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:8241177 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:8241177 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:8241177 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:8241177 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:8241177 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:8241177 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:8241177 | pubmed:issn | 0006-2960 | lld:pubmed |
| pubmed-article:8241177 | pubmed:author | pubmed-author:BurkaJ FJF | lld:pubmed |
| pubmed-article:8241177 | pubmed:author | pubmed-author:FreyP APA | lld:pubmed |
| pubmed-article:8241177 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:8241177 | pubmed:day | 7 | lld:pubmed |
| pubmed-article:8241177 | pubmed:volume | 32 | lld:pubmed |
| pubmed-article:8241177 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:8241177 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:8241177 | pubmed:pagination | 13220-30 | lld:pubmed |
| pubmed-article:8241177 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
| pubmed-article:8241177 | pubmed:meshHeading | pubmed-meshheading:8241177-... | lld:pubmed |
| pubmed-article:8241177 | pubmed:meshHeading | pubmed-meshheading:8241177-... | lld:pubmed |
| pubmed-article:8241177 | pubmed:meshHeading | pubmed-meshheading:8241177-... | lld:pubmed |
| pubmed-article:8241177 | pubmed:meshHeading | pubmed-meshheading:8241177-... | lld:pubmed |
| pubmed-article:8241177 | pubmed:meshHeading | pubmed-meshheading:8241177-... | lld:pubmed |
| pubmed-article:8241177 | pubmed:meshHeading | pubmed-meshheading:8241177-... | lld:pubmed |
| pubmed-article:8241177 | pubmed:meshHeading | pubmed-meshheading:8241177-... | lld:pubmed |
| pubmed-article:8241177 | pubmed:meshHeading | pubmed-meshheading:8241177-... | lld:pubmed |
| pubmed-article:8241177 | pubmed:meshHeading | pubmed-meshheading:8241177-... | lld:pubmed |
| pubmed-article:8241177 | pubmed:meshHeading | pubmed-meshheading:8241177-... | lld:pubmed |
| pubmed-article:8241177 | pubmed:meshHeading | pubmed-meshheading:8241177-... | lld:pubmed |
| pubmed-article:8241177 | pubmed:meshHeading | pubmed-meshheading:8241177-... | lld:pubmed |
| pubmed-article:8241177 | pubmed:meshHeading | pubmed-meshheading:8241177-... | lld:pubmed |
| pubmed-article:8241177 | pubmed:year | 1993 | lld:pubmed |
| pubmed-article:8241177 | pubmed:articleTitle | The importance of binding energy in catalysis of hydride transfer by UDP-galactose 4-epimerase: a 13C and 15N NMR and kinetic study. | lld:pubmed |
| pubmed-article:8241177 | pubmed:affiliation | Institute for Enzyme Research, Graduate School, University of Wisconsin-Madison 53705. | lld:pubmed |
| pubmed-article:8241177 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:8241177 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:8241177 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| pubmed-article:8241177 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| entrez-gene:945354 | entrezgene:pubmed | pubmed-article:8241177 | lld:entrezgene |
