5 research outputs found
Основні підходи до розроблення дизайну упаковки
Упаковка – останній призов, який бачить покупець, і останній шанс
переконати його купити товар [1], тому над розробленням цікавого,
оригінального дизайну упаковки працює ціла армія професіоналів.
Дизайн упаковки включає гармонічну сукупність таких елементів, як:
форма, матеріал, розміри, якість виготовлення, вид друку, кольори
Modulation of Structure and Dynamics by Disulfide Bond Formation in Unfolded States
During oxidative folding, the formation of disulfide
bonds has
profound effects on guiding the protein folding pathway. Until now,
comparatively little is known about the changes in the conformational
dynamics in folding intermediates of proteins that contain only a
subset of their native disulfide bonds. In this comprehensive study,
we probe the conformational landscape of non-native states of lysozyme
containing a single native disulfide bond utilizing nuclear magnetic
resonance (NMR) spectroscopy, small-angle X-ray scattering (SAXS),
circular dichroism (CD) data, and modeling approaches. The impact
on conformational dynamics varies widely depending on the loop size
of the single disulfide variants and deviates significantly from random
coil predictions for both NMR and SAXS data. From these experiments,
we conclude that the introduction of single disulfides spanning a
large portion of the polypeptide chain shifts the structure and dynamics
of hydrophobic core residues of the protein so that these regions
exhibit levels of order comparable to the native state on the nanosecond
time scale
Seven Cysteine-Deficient Mutants Depict the Interplay between Thermal and Chemical Stabilities of Individual Cysteine Residues in Mitogen-Activated Protein Kinase c‑Jun N‑Terminal Kinase 1
Intracellular proteins can have free cysteines that may
contribute to their structure, function, and stability; however, free
cysteines can lead to chemical instabilities in solution because of
oxidation-driven aggregation. The MAP kinase, c-Jun N-terminal kinase
1 (JNK1), possesses seven free cysteines and is an important drug
target for autoimmune diseases, cancers, and apoptosis-related diseases.
To characterize the role of cysteine residues in the structure, function,
and stability of JNK1, we prepared and evaluated wild-type JNK1 and
seven cysteine-deficient JNK1 proteins. The nonreduced sodium dodecyl
sulfate–polyacrylamide gel electrophoresis experiments showed
that the chemical stability of JNK1 increased as the number of cysteines
decreased. The contribution of each cysteine residue to biological
function and thermal stability was highly susceptible to the environment
surrounding the particular cysteine mutation. The mutations of solvent-exposed
cysteine to serine did not influence biological function and increased
the thermal stability. The mutation of the accessible cysteine involved
in the hydrophobic pocket did not affect biological function, although
a moderate thermal destabilization was observed. Cysteines in the
loosely
assembled hydrophobic environment moderately contributed to thermal
stability, and the mutations of these cysteines had a negligible effect
on enzyme activity. The other cysteines are involved in the tightly
filled hydrophobic core, and mutation of these residues was found
to correlate with thermal stability and enzyme activity. These findings
about the role of cysteine residues should allow us to obtain a stable
JNK1 and thus promote the discovery of potent JNK1 inhibitors
Modulation of Structure and Dynamics by Disulfide Bond Formation in Unfolded States
During oxidative folding, the formation of disulfide
bonds has
profound effects on guiding the protein folding pathway. Until now,
comparatively little is known about the changes in the conformational
dynamics in folding intermediates of proteins that contain only a
subset of their native disulfide bonds. In this comprehensive study,
we probe the conformational landscape of non-native states of lysozyme
containing a single native disulfide bond utilizing nuclear magnetic
resonance (NMR) spectroscopy, small-angle X-ray scattering (SAXS),
circular dichroism (CD) data, and modeling approaches. The impact
on conformational dynamics varies widely depending on the loop size
of the single disulfide variants and deviates significantly from random
coil predictions for both NMR and SAXS data. From these experiments,
we conclude that the introduction of single disulfides spanning a
large portion of the polypeptide chain shifts the structure and dynamics
of hydrophobic core residues of the protein so that these regions
exhibit levels of order comparable to the native state on the nanosecond
time scale
Modulation of Structure and Dynamics by Disulfide Bond Formation in Unfolded States
During oxidative folding, the formation of disulfide
bonds has
profound effects on guiding the protein folding pathway. Until now,
comparatively little is known about the changes in the conformational
dynamics in folding intermediates of proteins that contain only a
subset of their native disulfide bonds. In this comprehensive study,
we probe the conformational landscape of non-native states of lysozyme
containing a single native disulfide bond utilizing nuclear magnetic
resonance (NMR) spectroscopy, small-angle X-ray scattering (SAXS),
circular dichroism (CD) data, and modeling approaches. The impact
on conformational dynamics varies widely depending on the loop size
of the single disulfide variants and deviates significantly from random
coil predictions for both NMR and SAXS data. From these experiments,
we conclude that the introduction of single disulfides spanning a
large portion of the polypeptide chain shifts the structure and dynamics
of hydrophobic core residues of the protein so that these regions
exhibit levels of order comparable to the native state on the nanosecond
time scale