Conformational change of the methionine 20 loop of Escherichia coli dihydrofolate reductase modulates pKa of the bound dihydrofolate.

Conformational change of the methionine 20 loop of Escherichia coli dihydrofolate reductase modulates pKa of the bound dihydrofolate. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Conformational change of the methionine 20 loop of Escherichia coli dihydrofolate reductase modulates pKa of the bound dihydrofolate. Abstract Text:

Ilja V Khavrutskii,Daniel J Price,Jinhyuk Lee,Charles L Brooks,

We evaluate the pK(a) of dihydrofolate (H(2)F) at the N(5) position in three ternary complexes with Escherichia coli dihydrofolate reductase (ecDHFR), namely ecDHFR(NADP(+):H(2)F) in the closed form (1), and the Michaelis complexes ecDHFR(NADPH:H(2)F) in the closed (2) and occluded (3) forms, by performing free energy perturbation with molecular dynamics simulations (FEP/MD). Our simulations suggest that in the Michaelis complex the pK(a) is modulated by the Met20 loop fluctuations, providing the largest pK(a) shift in substates with a "tightly closed" loop conformation; in the "partially closed/open" substates, the pK(a) is similar to that in the occluded complex. Conducive to the protonation, tightly closing the Met20 loop enhances the interactions of the cofactor and the substrate with the Met20 side chain and aligns the nicotinamide ring of the cofactor coplanar with the pterin ring of the substrate. Overall, the present study favors the hypothesis that N(5) is protonated directly from solution and provides further insights into the mechanism of the substrate protonation.

Conformational change of the methionine 20 loop of Escherichia coli dihydrofolate reductase modulates pKa of the bound dihydrofolate. Publishing Authors By Initials

IV Khavrutskii,DJ Price,J Lee,CL Brooks,

For similar enzymes and coenzymes: enzymes: oxidoreductases: oxidoreductases acting on ch-nh group donors: tetrahydrofolate dehydrogenase research abstracts see: enzymes and coenzymes: enzymes: oxidoreductases: oxidoreductases acting on ch-nh group donors: tetrahydrofolate dehydrogenase research

PUBMED ID PMID:

MEDLINE DATE:

Conformational change of the methionine 20 loop of Escherichia coli dihydrofolate reductase modulates pKa of the bound dihydrofolate. Journal Published:

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

Journal: Protein science : a publication of the Protein Soc

VOLUME: 16

Page Numbers: 1087-100

Journal Abbreviation: Protein Sci.

ISSN: 0961-8368

DAY: 1

MONTH: 05

YEAR: 2007

Conformational change of the methionine 20 loop of Escherichia coli dihydrofolate reductase modulates pKa of the bound dihydrofolate. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9211750

Conformational change of the methionine 20 loop of Escherichia coli dihydrofolate reductase modulates pKa of the bound dihydrofolate. Keywords Mesh Terms:

KEYWORDS: Tetrahydrofolate Dehydrogenase

MESH TERMS: metabolism

Chemical & Substance for Abstract: Conformational change of the methionine 20 loop of Escherichia coli dihydrofolate reductase modulates pKa of the bound dihydrofolate. Information

Substance Name: Tetrahydrofolate Dehydrogenase

Registry Number: EC 1.5.1.3

Grant and Affiliation Information for Conformational change of the methionine 20 loop of Escherichia coli dihydrofolate reductase modulates pKa of the bound dihydrofolate.

AFFILIATION: The Scripps Research Institute, Department of Molecular Biology, TPC6, La Jolla, California 92037, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM57513

ACRONYM: GM

MEDLINETA: Protein Sci

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Conformational change of the methionine 20 loop of Escherichia coli dihydrofolate reductase modulates pKa of the bound dihydrofolate Related Publications

• A flow injection system with in-series ultraviolet and electrochemical detection for the simultaneous determination of lovastatin and butylated hydroxyanisole in a tablet.
• A line integral reaction path approximation for large systems via nonlinear constrained optimization: application to alanine dipeptide and the beta hairpin of protein G.
• A modified TIP3P water potential for simulation with Ewald summation.
• A mouse model of sensorimotor controlled cortical impact: characterization using longitudinal magnetic resonance imaging, behavioral assessments and histology.
• A nonadditive methanol force field: bulk liquid and liquid-vapor interfacial properties via molecular dynamics simulations using a fluctuating charge model.
• A radioimmunoassay for the metabolites of the anabolic steroid nandrolone.
• AT(1) and glutamatergic receptors in paraventricular nucleus support blood pressure during water deprivation.
• Addressing asthma in Texas: development of a school-based asthma surveillance program for Texas elementary schools.
• Adjacent gauche stabilization in linear alkanes: implications for polymer models and conformational analysis.
• Can molecular dynamics simulations provide high-resolution refinement of protein structure?
• Contributions of working muscle to whole body lipid metabolism are altered by exercise intensity and training.
• Critical importance of length-scale dependence in implicit modeling of hydrophobic interactions.
• Deciphering the kinetic mechanism of spontaneous self-assembly of icosahedral capsids.
• Developmental expression of myostatin in cardiomyocytes and its effect on foetal and neonatal rat cardiomyocyte proliferation.
• Disruption of endothelial cell interactions with the novel HU177 cryptic collagen epitope inhibits angiogenesis.
• Exploring atomistic details of pH-dependent peptide folding.
• Folding intermediate in the villin headpiece domain arises from disruption of a N-terminal hydrogen-bonded network.
• Harmonic Fourier beads method for studying rare events on rugged energy surfaces.
• Hydrophobic cooperativity as a mechanism for amyloid nucleation.
• Inhibition of angiogenesis and tumor metastasis by targeting a matrix immobilized cryptic extracellular matrix epitope in laminin.
• Lactate: link between glycolytic and oxidative metabolism.
• Magnetic resonance spectroscopy detects brain injury and predicts cognitive functioning in children with brain injuries.
• Membrane assembly of simple helix homo-oligomers studied via molecular dynamics simulations.
• Nitric oxide impairs baroreflex gain during acute psychological stress.
• Prediction of dermal absorption from complex chemical mixtures: incorporation of vehicle effects and interactions into a QSPR framework.
• Relationships between person and health factors and job characteristics in women with systemic lupus erythematosus.
• Revisiting the hexane-water interface via molecular dynamics simulations using nonadditive alkane-water potentials.
• Selenomethionine induced transcriptional programs in human prostate cancer cells.
• Validity of self-reported health plan information in a population-based health survey.
• Where do all the maternal effects go? Variation in offspring body size through ontogeny in the live-bearing fish Poecilia parae.