Determinants of substrate specificity for saccharopine dehydrogenase from Saccharomyces cerevisiae.

Determinants of substrate specificity for saccharopine dehydrogenase from Saccharomyces cerevisiae. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Determinants of substrate specificity for saccharopine dehydrogenase from Saccharomyces cerevisiae. Abstract Text:

Hengyu Xu,Ann H West,Paul F Cook,

A survey of NADH, alpha-Kg, and lysine analogues has been undertaken in an attempt to define the substrate specificity of saccharopine dehydrogenase and to identify functional groups on all substrates and dinucleotides important for substrate binding. A number of NAD analogues, including NADP, 3-acetylpyridine adenine dinucleotide (3-APAD), 3-pyridinealdehyde adenine dinucleotide (3-PAAD), and thionicotinamide adenine dinucleotide (thio-NAD), can serve as a substrate in the oxidative deamination reaction, as can a number of alpha-keto analogues, including glyoxylate, pyruvate, alpha-ketobutyrate, alpha-ketovalerate, alpha-ketomalonate, and alpha-ketoadipate. Inhibition studies using nucleotide analogues suggest that the majority of the binding energy of the dinucleotides comes from the AMP portion and that distinctly different conformations are generated upon binding of the oxidized and reduced dinucleotides. Addition of the 2'-phosphate as in NADPH causes poor binding of subsequent substrates but has little effect on coenzyme binding and catalysis. In addition, the 10-fold decrease in affinity of 3-APAD in comparison to NAD suggests that the nicotinamide ring binding pocket is hydrophilic. Extensive inhibition studies using aliphatic and aromatic keto acid analogues have been carried out to gain insight into the keto acid binding pocket. Data suggest that a side chain with three carbons (from the alpha-keto group up to and including the side chain carboxylate) is optimal. In addition, the distance between the C1-C2 unit and the C5 carboxylate of the alpha-keto acid is also important for binding; the alpha-oxo group contributes a factor of 10 to affinity. The keto acid binding pocket is relatively large and flexible and can accommodate the bulky aromatic ring of a pyridine dicarboxylic acid and a negative charge at the C3 but not the C4 position. However, the amino acid binding site is hydrophobic, and the optimal length of the hydrophobic portion of the amino acid carbon side chain is three or four carbons. In addition, the amino acid binding pocket can accommodate a branch at the gamma-carbon, but not at the beta-carbon.

Determinants of substrate specificity for saccharopine dehydrogenase from Saccharomyces cerevisiae. Publishing Authors By Initials

H Xu,AH West,PF Cook,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: substrate specificity research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: substrate specificity research

PUBMED ID PMID:

MEDLINE DATE:

Determinants of substrate specificity for saccharopine dehydrogenase from Saccharomyces cerevisiae. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Biochemistry

VOLUME: 46

Page Numbers: 7625-36

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 2

MONTH: 06

YEAR: 2007

Determinants of substrate specificity for saccharopine dehydrogenase from Saccharomyces cerevisiae. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370623

Determinants of substrate specificity for saccharopine dehydrogenase from Saccharomyces cerevisiae. Keywords Mesh Terms:

KEYWORDS: Substrate Specificity

MESH TERMS: metabolism

Chemical & Substance for Abstract: Determinants of substrate specificity for saccharopine dehydrogenase from Saccharomyces cerevisiae. Information

Substance Name: Saccharopine Dehydrogenases

Registry Number: EC 1.5.1.-

Grant and Affiliation Information for Determinants of substrate specificity for saccharopine dehydrogenase from Saccharomyces cerevisiae.

AFFILIATION: Department of Chemistry and Biochemistry, University of Oklahoma, 620 Parrington Oval, Norman, Oklahoma 73019, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM 071417

ACRONYM: GM

MEDLINETA: Biochemistry

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Determinants of substrate specificity for saccharopine dehydrogenase from Saccharomyces cerevisiae Related Publications

• 449.
• 5-HTTLPR Genotype-Specific Phenotype in Children and Adolescents With Autism.
• A proposed proton shuttle mechanism for saccharopine dehydrogenase from Saccharomyces cerevisiae.
• A prospective, open-label trial of memantine in the treatment of cognitive, behavioral, and memory dysfunction in pervasive developmental disorders.
• An intracrine view of angiogenesis.
• Association of dopamine transporter genotype with disruptive behavior disorders in an eight-year longitudinal study of children and adolescents.
• Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism.
• Beta-arrestins 1 and 2 differentially regulate LPS-induced signaling and pro-inflammatory gene expression.
• Characterization and in vitro degradation of salicylate-derived poly(anhydride-ester microspheres).
• Chronic glaucoma case finding and treatment in rural Africa: some questions and answers.
• Complete kinetic mechanism of homoisocitrate dehydrogenase from Saccharomyces cerevisiae.
• Conformational analysis of the cis- and trans-adducts of the Pictet - Spengler reaction. Evidence for the structural basis for the C(1) - N(2) scission process in the cis- to trans-isomerization.
• Differential regulation of lipopolysaccharide and Gram-positive bacteria induced cytokine and chemokine production in splenocytes by Galphai proteins.
• Effect of Medicaid Managed Care on racial disparities in health care access.
• First enantiospecific total synthesis of the important biogenetic intermediates, (+)-polyneuridine and (+)-polyneuridine aldehyde, as well as 16-epi-vellosimine and macusine A.
• Genes expressed by both mesangial cells and bone marrow-derived cells underlie genetic susceptibility to crescentic glomerulonephritis in the rat.
• How to improve the outcome of cataract surgery.
• ITGB3 shows genetic and expression interaction with SLC6A4.
• Improving point predictions of random effects for subjects at high risk.
• Imputation strategies for blood pressure data nonignorably missing due to medication use.
• Monitoring cataract surgical outcomes: 'hand written' registration method.
• Oxidation artifacts in the electrospray mass spectrometry of Abeta Peptide.
• Pharmacological studies with a nonpeptidic, delta-opioid (-)-(1R,5R,9R)-5,9-dimethyl-2'-hydroxy-2-(6-hydroxyhexyl)-6,7-benzomorphan hydrochloride ((-)-NIH 11082).
• Preventing alcohol-exposed pregnancies.
• Remarkably mild and efficient intramolecular Friedel-Crafts cyclization catalyzed by In(III).
• The effects of dietary protein on age and weight at the onset of puberty in Brown Swiss and Zebu heifers in the tropics.
• The molecular mechanisms responsible for resistance in plant-pathogen interactions of the gene-for-gene type function more broadly than previously imagined.
• Tremor/ataxia syndrome and fragile X premutation: diagnostic caveats.
• Walking stride variability on different walking surfaces: 849: june 1 2:00 PM - 2:15 PM.
• rasiRNAs, DNA damage, and embryonic axis specification.