Function of a conserved loop of the beta-domain, not involved in thiamin diphosphate binding, in catalysis and substrate activation in yeast pyruvate decarboxylase.

Function of a conserved loop of the beta-domain, not involved in thiamin diphosphate binding, in catalysis and substrate activation in yeast pyruvate decarboxylase. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Function of a conserved loop of the beta-domain, not involved in thiamin diphosphate binding, in catalysis and substrate activation in yeast pyruvate decarboxylase. Abstract Text:

Ebenezer Joseph,Wen Wei,Kai Tittmann,Frank Jordan,

The X-ray crystal structure of pyruvamide-activated yeast pyruvate decarboxylase (YPDC) revealed a flexible loop spanning residues 290 to 304 on the beta-domain of the enzyme, not seen in the absence of pyruvamide, a substrate activator surrogate. Site-directed mutagenesis studies revealed that residues on the loop affect the activity, with some residues reducing k(cat)/K(m) by at least 1000-fold. In the pyruvamide-activated form, the loop located on the beta domain can transfer information to the active center thiamin diphosphate (ThDP) located at the interface of the alpha and gamma domains. The sigmoidal v(0)-[S] curve with wild-type YPDC attributed to substrate activation is modulated for most variants, but is not abolished. Pre-steady-state stopped-flow studies for product formation on these loop variants provided evidence for three enzyme conformations connected by two transitions, as already noted for the wild-type YPDC at pH 5.0 [Sergienko, E. A., and Jordan, F. (2002) Biochemistry 41, 3952-3967]. (1)H NMR analysis of the intermediate distribution resulting from acid quench [Tittmann et al. (2003) Biochemistry 42, 7885-7891] with all YPDC variants indicated that product release is rate limiting in the steady state. Apparently, the loop is not solely responsible for the substrate activation behavior, rather it may affect the behavior of residue C221 identified as the trigger for substrate activation. The most important function of the loop is to control the conformational equilibrium between the "open" and "closed" conformations of the enzyme identified in the pyruvamide-activated structure [Lu et al. (2000) Eur. J. Biochem. 267, 861-868].

Function of a conserved loop of the beta-domain, not involved in thiamin diphosphate binding, in catalysis and substrate activation in yeast pyruvate decarboxylase. Publishing Authors By Initials

E Joseph,W Wei,K Tittmann,F Jordan,

For similar thiazoles: thiamine: thiamine pyrophosphate research abstracts see: thiazoles: thiamine: thiamine pyrophosphate research

PUBMED ID PMID:

MEDLINE DATE:

Function of a conserved loop of the beta-domain, not involved in thiamin diphosphate binding, in catalysis and substrate activation in yeast pyruvate decarboxylase. Journal Published:

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

Journal: Biochemistry

VOLUME: 45

Page Numbers: 13517-27

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 14

MONTH: Nov

YEAR: 2006

Function of a conserved loop of the beta-domain, not involved in thiamin diphosphate binding, in catalysis and substrate activation in yeast pyruvate decarboxylase. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370623

Function of a conserved loop of the beta-domain, not involved in thiamin diphosphate binding, in catalysis and substrate activation in yeast pyruvate decarboxylase. Keywords Mesh Terms:

KEYWORDS: Thiamine Pyrophosphate

MESH TERMS: metabolism

Chemical & Substance for Abstract: Function of a conserved loop of the beta-domain, not involved in thiamin diphosphate binding, in catalysis and substrate activation in yeast pyruvate decarboxylase. Information

Substance Name: Pyruvate Decarboxylase

Registry Number: EC 4.1.1.1

Grant and Affiliation Information for Function of a conserved loop of the beta-domain, not involved in thiamin diphosphate binding, in catalysis and substrate activation in yeast pyruvate decarboxylase.

AFFILIATION: Department of Chemistry, Rutgers, the State University of New Jersey, Newark, New Jersey 07102, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM-50380

ACRONYM: GM

MEDLINETA: Biochemistry

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Function of a conserved loop of the beta-domain, not involved in thiamin diphosphate binding, in catalysis and substrate activation in yeast pyruvate decarboxylase Related Publications

• 2-Methoxyestradiol suppresses microtubule dynamics and arrests mitosis without depolymerizing microtubules.
• A laser-temperature-jump method for the study of the rate of transfer of hydrophobic ions and carriers across the interface of thin lipid membranes.
• Acetylphosphinate is the most potent mechanism-based substrate-like inhibitor of both the human and Escherichia coli pyruvate dehydrogenase components of the pyruvate dehydrogenase complex.
• Androgen-sensitivity of somata and dendrites of spinal nucleus of the bulbocavernosus (SNB) motoneurons in male C57BL6J mice.
• Beyond raloxifene for the prevention of osteoporosis and breast cancer.
• Cooperative effect of gefitinib and fumitremorgin c on cell growth and chemosensitivity in estrogen receptor alpha negative fulvestrant-resistant MCF-7 cells.
• Current noise in transport of hydrophobic ions through lipid bilayer membranes including diffusion polarization in the aqueous phase.
• Development of a one-step immunocapture real-time TaqMan RT-PCR assay for the broad spectrum detection of Pepino mosaic virus.
• Dexamethasone in acute bacterial meningitis.
• Effect of raloxifene on salivary sex steroid concentrations in premenopausal women.
• Effects of the testicular feminization mutation (tfm) of the androgen receptor gene on BSTMPM volume and morphology in rats.
• Function of a conserved loop of the beta-domain, not involved in thiamin diphosphate binding, in catalysis and substrate activation in yeast pyruvate decarboxylase.
• Interpretation of serum C-reactive protein (CRP) levels for cardiovascular disease risk is complicated by race, pulmonary disease, body mass index, gender, and osteoarthritis.
• Leaf maximum photosynthetic rate and venation are linked by hydraulics.
• Molecular basis of acute intermittent porphyria.
• Optimising endocrine approaches for the chemoprevention of breast cancer beyond the Study of Tamoxifen and Raloxifene (STAR) trial.
• Origin and evolution of human microRNAs from transposable elements.
• Peripheral endothelin A receptor antagonism attenuates carcinoma-induced pain.
• Racial disparity in stage at diagnosis and survival among adults with oral cancer in the US.
• Randomised, placebo-controlled, double-blind study to investigate the efficacy and safety of the acute use of sodium picosulphate in patients with chronic constipation.
• Relationship of limb length inequality with radiographic knee and hip osteoarthritis.
• Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer.
• SERMs: meeting the promise of multifunctional medicines.
• Spirituality and depressive symptoms in a racially diverse US sample of community-dwelling adults.
• Steroid receptors and their role in the biology and control of breast cancer growth.
• Synthesis with good enantiomeric excess of both enantiomers of alpha-ketols and acetolactates by two thiamin diphosphate-dependent decarboxylases.
• The 1',4'-iminopyrimidine tautomer of thiamin diphosphate is poised for catalysis in asymmetric active centers on enzymes.
• Tuning a potassium channel--the caress of the surroundings.
• Use of polymerase chain reaction as a diagnostic tool for neonatal sepsis can result in a decrease in use of antibiotics and total neonatal intensive care unit length of stay.
• Validity and factor structure of the AUSCAN Osteoarthritis Hand Index in a community-based sample.