Linked Life Data

11790142

Source:http://linkedlifedata.com/resource/pubmed/id/11790142

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-1-15
pubmed:abstractText
K(m) and V(max) values for 10 coenzyme analogs never previously studied with any aldehyde dehydrogenase and NADP(+) were compared with those for NAD(+) for three human aldehyde dehydrogenases (EC 1.2.1.3); the cytoplasmic E1 (the product of the aldh1 gene), the mitochondrial E2 (the product of the aldh2 gene) and the cytoplasmic E3 (the product of the aldh9 gene) isozymes. Structural information on changes in coenzyme-protein interactions were obtained via molecular dynamics (MD) studies with the E2 isozyme and quantum mechanical (QM) calculations were used to study changes in charge distribution of the pyridine ring and relative free energies of solvation of the purine ring in the analogs. E1 showed the broadest substrate specificity and was the only isozyme subject to substrate inhibition, both of which are suggested to be due to the two coenzyme conformations observed previously in the sheep crystal structure. NADP(+) selectivity is indicated to be influenced by Glu195 in E1 and E2. Substitutions in the purine ring affected K(m) but not V(max), with the changes in K(m) being dominated by the hydrophobicity of the purine ring as indicted by the QM calculations. Substitutions in the pyridine ring sometimes rendered the coenzymes inactive, with no consistent pattern observed for the three coenzymes. Structural analysis of the coenzyme analog-E2 MD simulations revealed different structural perturbations of the surrounding active site, though interactions with Asn169 and Glu399 were preserved in all cases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0739-1102
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
429-47
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Human aldehyde dehydrogenase catalytic activity and structural interactions with coenzyme analogs.
pubmed:affiliation
Center for Alcohol Studies and Department of Molecular Biology and Biochemistry, Rutgers The State University of New Jersey, Piscataway, NJ 08854- 8001, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.