Journal of Chemical Information and Modeling,
Год журнала:
2019,
Номер
59(9), С. 3803 - 3816
Опубликована: Авг. 6, 2019
We
developed
and
validated
a
novel
force
field
in
the
context
of
AMBER
parameterization
for
simulation
zinc(II)-binding
proteins.
The
proposed
assumes
nonbonded
spherical
interactions
between
central
zinc(II)
coordinating
residues.
A
crucial
innovative
aspect
our
approach
is
to
account
polarization
effects
cation
by
redefining
atomic
charges
residues
an
adjustment
Lennard-Jones
parameters
Zn-interacting
atoms
reproduce
mean
distance
distributions.
optimal
transferable
parametrization
was
obtained
performing
accurate
quantum
mechanical
calculations
on
training
set
high-quality
protein
structures,
encompassing
most
common
folds
sites.
addressed
sites
contain
ion
tetra-coordinated
histidine
cysteine
represent
about
70%
all
physiologically
relevant
Protein
Data
Bank.
Molecular
dynamics
simulations
with
explicit
solvent,
carried
out
several
proteins
not
included
set,
show
that
model
preserves
tetra-coordination
metal
site
remarkable
stability,
yielding
zinc(II)-X
distances
similar
experimental
data.
Finally,
tested
evaluating
affinities,
using
alchemical
free
energy
perturbation
approach.
calculated
dissociation
constants
correlate
satisfactorily
counterpart
demonstrating
validity
transferability
Aqueous
zinc-ion
batteries
hold
attractive
potential
for
large-scale
energy
storage
devices
owing
to
their
prominent
electrochemical
performance
and
high
security.
Nevertheless,
the
applications
of
aqueous
electrolytes
have
generated
various
challenges,
including
uncontrolled
dendrite
growth
parasitic
reactions,
thereby
deteriorating
Zn
anode's
stability.
Herein,
inspired
by
superior
affinity
between
Zn2+
amino
acid
chains
in
zinc
finger
protein,
a
cost-effective
green
glycine
additive
is
incorporated
into
stabilize
anode.
As
confirmed
experimental
characterizations
theoretical
calculations,
additives
can
not
only
reorganize
solvation
sheaths
hydrated
via
partial
substitution
coordinated
H2
O
but
also
preferentially
adsorb
onto
anode,
significantly
restraining
interfacial
side
reactions.
Accordingly,
anode
could
realize
long
lifespan
over
2000
h
enhanced
reversibility
(98.8%)
glycine-containing
electrolyte.
Furthermore,
assembled
Zn||α-MnO2
full
cells
with
glycine-modified
electrolyte
delivers
substantial
capacity
retention
(82.3%
after
1000
cycles
at
2
A
g-1
),
showing
promising
application
prospects.
This
innovative
bio-inspired
design
concept
would
inject
new
vitality
development
electrolytes.
Chemical Reviews,
Год журнала:
2021,
Номер
121(23), С. 14594 - 14648
Опубликована: Окт. 15, 2021
The
functions,
purposes,
and
roles
of
metallothioneins
have
been
the
subject
speculations
since
discovery
protein
over
60
years
ago.
This
article
guides
through
history
investigations
resolves
multiple
contentions
by
providing
new
interpretations
structure-stability-function
relationship.
It
challenges
dogma
that
biologically
relevant
structure
mammalian
proteins
is
only
one
determined
X-ray
diffraction
NMR
spectroscopy.
terms
metallothionein
thionein
are
ambiguous
insufficient
to
understand
biological
function.
need
be
seen
in
their
context,
which
limits
defines
chemistry
possible.
They
exist
forms
with
different
degrees
metalation
types
metal
ions.
homoleptic
thiolate
coordination
important
for
molecular
mechanism.
endows
redox
activity
a
specific
pH
dependence
affinities.
proteins,
therefore,
also
states
sulfur
donor
ligands.
Their
dynamics
allows
vast
conformational
landscape
interactions
other
Many
fundamental
signal
transduction
pathways
regulate
expression
dozen
human
genes.
Recent
advances
understanding
control
cellular
zinc
copper
homeostasis
foundation
suggesting
provide
highly
dynamic,
regulated,
uniquely
buffer
availability,
fluctuations,
signaling
transients
most
competitive
Zn(II)
Cu(I)
ions
space
time.
Nucleic Acids Research,
Год журнала:
2020,
Номер
48(22), С. 12534 - 12555
Опубликована: Ноя. 7, 2020
Guanine-quadruplexes
(G4s)
are
non-canonical
four-stranded
structures
that
can
be
formed
in
guanine
(G)
rich
nucleic
acid
sequences.
A
great
number
of
G-rich
sequences
capable
forming
G4
have
been
described
based
on
vitro
analysis,
and
evidence
supporting
their
formation
live
cells
continues
to
accumulate.
While
DNA
G4s
(dG4s)
within
chromatin
vivo
has
supported
by
different
chemical,
imaging
genomic
approaches,
RNA
(rG4s)
remains
a
matter
discussion.
Recent
data
support
the
dynamic
nature
transcriptome.
Such
fluctuation
rG4
folding-unfolding
underpins
biological
significance
these
regulation
metabolism.
Moreover,
rG4-mediated
functions
may
ultimately
connected
mechanisms
underlying
disease
pathologies
and,
potentially,
provide
novel
options
for
therapeutics.
In
this
framework,
we
will
review
landscape
rG4s
transcriptome,
focus
potential
impact
processes,
consider
an
emerging
connection
human
health
disease.
Chemical Research in Toxicology,
Год журнала:
2020,
Номер
33(3), С. 709 - 726
Опубликована: Янв. 28, 2020
Exposure
to
arsenic
in
contaminated
drinking
water
is
an
emerging
public
health
problem
that
impacts
more
than
200
million
people
worldwide.
Accumulating
lines
of
evidence
from
epidemiological
studies
revealed
chronic
exposure
can
result
various
human
diseases
including
cancer,
type
2
diabetes,
and
neurodegenerative
disorders.
Arsenic
also
classified
as
a
Group
I
carcinogen.
In
this
review,
we
survey
extensively
different
modes
action
for
arsenic-induced
carcinogenesis,
with
focus
being
placed
on
arsenic-mediated
impairment
DNA
repair
pathways.
Inorganic
be
bioactivated
by
methylation,
the
ensuing
products
are
highly
genotoxic.
Bioactivation
arsenicals
elicits
production
reactive
oxygen
nitrogen
species
(ROS
RNS),
which
directly
damage
modify
cysteine
residues
proteins.
Results
recent
suggest
zinc
finger
proteins
crucial
molecular
targets
direct
binding
As3+
or
modifications
ROS/RNS,
may
constitute
common
mechanism
underlying
perturbations
repair.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Янв. 5, 2021
Abstract
p97,
also
known
as
valosin-containing
protein
(VCP)
or
Cdc48,
plays
a
central
role
in
cellular
homeostasis.
Human
p97
mutations
are
associated
with
several
neurodegenerative
diseases.
Targeting
and
its
cofactors
is
strategy
for
cancer
drug
development.
Despite
significant
structural
insights
into
the
fungal
homolog
little
about
how
human
interacts
cofactors.
Recently,
anti-alcohol
abuse
disulfiram
was
found
to
target
through
Npl4,
cofactor
of
but
molecular
mechanism
remains
elusive.
Here,
using
single-particle
cryo-electron
microscopy
(cryo-EM),
we
uncovered
three
Npl4
conformational
states
complex
before
ATP
hydrolysis.
The
motion
results
from
zinc
finger
motifs
interacting
N
domain
which
essential
unfolding
activity
p97.
In
vitro
cell-based
assays
showed
that
derivative
bis-(diethyldithiocarbamate)-copper
(CuET)
can
bypass
copper
transporter
system
inhibit
function
cytoplasm
by
releasing
cupric
ions
under
oxidative
conditions,
disrupt
locking
switch
complex.
