Biochemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 19, 2025
The
catalytic
efficiency
of
acetylcholinesterase
(AChE)
is
likely
regulated
by
the
protonation
states
and
conformational
adaptations
its
residues.
While
neonicotinoid
insecticides
are
recognized
for
impairing
AChE
function
through
neurotoxic
mechanisms,
precise
molecular
mechanisms
governing
this
inhibition
remain
poorly
characterized.
This
investigation
elucidates
how
structural
variations
among
neonicotinoids
modulate
equilibria
Glu-202
His-447
in
AChE's
triad.
Comparative
analysis
reveals
that
nitro-substituted
(imidacloprid,
clothianidin)
induce
more
pronounced
state
transitions
compared
to
their
cyano-containing
counterparts
(thiacloprid,
acetamiprid).
Specifically,
strong
electron-withdrawing
nitro
groups
facilitate
conversion
from
deprotonation
(GLU)
(GLH)
δ-
(HID)
ε-position
(HIE)
enhanced
electrostatic
interactions.
These
electronic
perturbations
trigger
reorganization
within
active
site,
evidenced
group-directed
residue
realignment
subsequent
H-bond
formation.
Energy
decomposition
identifies
contributions
as
primary
determinant
binding
affinity
differences,
with
nitro-neonicotinoids
exhibiting
stronger
interactions
than
cyano-neonicotinoids.
QM/MM
metadynamics
substantial
alterations
disrupt
biocatalytic
function,
particularly
capacity
acetylcholine
hydrolysis.
Finally,
SH-SY5Y-based
cellular
assays
show
imidacloprid
exhibits
strongest
inhibitory
effect
on
intracellular
activity,
while
thiacloprid
acetamiprid
weaker
effects,
aligning
computational
predictions.
study
provides
insights
into
protonation-state-induced
mediated
neonicotinoids,
contributing
assessment
exogenous
ligand-induced
potential
ecological
human
health
risks.
Journal of Translational Medicine,
Journal Year:
2023,
Volume and Issue:
21(1)
Published: June 7, 2023
Abstract
Hepatocellular
carcinoma
(HCC)
is
the
leading
cause
of
cancer-related
death
in
people,
and
a
common
primary
liver
cancer.
Lacking
early
diagnosis
high
recurrence
rate
after
surgical
resection,
systemic
treatment
still
an
important
method
for
advanced
HCC.
Different
drugs
have
distinct
curative
effects,
side
effects
drug
resistance
due
to
different
properties.
At
present,
conventional
molecular
HCC
displayed
some
limitations,
such
as
adverse
reactions,
insensitivity
medicines,
resistance.
Noncoding
RNAs
(ncRNAs),
including
microRNAs
(miRNAs),
long
noncoding
(lncRNAs)
circular
(circRNAs),
been
well
documented
be
involved
occurrence
progression
Novel
biomarkers
therapeutic
targets,
research
into
basis
resistance,
are
urgently
needed
management
We
review
current
on
ncRNAs
consolidate
known
roles
regulating
examine
potential
clinical
applications
overcoming
barriers
based
targeted
therapy,
cell
cycle
non-specific
chemotherapy
specific
chemotherapy.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: June 22, 2023
Abstract
The
relationship
between
pH
and
enzyme
catalytic
activity,
especially
the
optimal
(pHopt)
at
which
enzymes
function,
is
critical
for
biotechnological
applications.
Hence,
computational
methods
to
predict
pHopt
will
enhance
discovery
design
by
facilitating
accurate
identification
of
that
function
optimally
specific
levels,
elucidating
sequence-function
relationships.
In
this
study,
we
proposed
evaluated
various
machine-learning
predicting
pHopt,
conducting
extensive
hyperparameter
optimization,
training
over
11,000
model
instances.
Our
results
demonstrate
models
utilizing
language
embeddings
markedly
outperform
other
in
pHopt.
We
present
EpHod,
best-performing
model,
making
it
publicly
available
researchers.
From
sequence
data,
EpHod
directly
learns
structural
biophysical
features
relate
including
proximity
residues
center
accessibility
solvent
molecules.
Overall,
presents
a
promising
advancement
prediction
potentially
speed
up
development
technologies.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(16)
Published: Feb. 22, 2024
Chemical
modifications
of
enzymes
excel
in
the
realm
enzyme
engineering
due
to
its
directness,
robustness,
and
efficiency;
however,
challenges
persist
devising
versatile
effective
strategies.
In
this
study,
we
introduce
a
supramolecular
modification
methodology
that
amalgamates
polymer
with
Candida
antarctica
lipase
B
(CalB)
create
(SupEnzyme).
This
approach
features
straightforward
preparation
amphiphilic
(β-CD@SMA),
which
was
subsequently
conjugated
enzyme,
resulting
SupEnzyme
capable
self-assembly
into
nanoparticles.
The
nanoparticles
can
form
micron-scale
aggregates
through
electrostatic
interactions
guest
entities,
thus
enhancing
catalyst
recycling.
Remarkably,
these
maintain
80
%
activity
after
seven
cycles,
outperforming
Novozym
435.
Additionally,
they
effectively
initiate
photobiocatalytic
cascade
reactions
using
photocatalysts.
As
consequence,
our
exhibits
noteworthy
adaptability
modification,
presenting
platform
for
various
polymer,
biocompatible
pairings,
potential
applications
fields
chemistry
biology.
Journal of the American Oil Chemists Society,
Journal Year:
2024,
Volume and Issue:
101(9), P. 839 - 850
Published: March 12, 2024
Abstract
Rhizopus
oryzae
lipase
(ROL)
is
known
to
present
high
selectivity
in
chemical
reactions.
However,
the
poor
stability
of
ROL
effectively
limits
its
industrial
applications.
In
this
study,
several
immobilization
protocols,
such
as
hydrophobic
adsorption,
covalent
immobilization,
multi‐point
attachment,
ionic
adsorption/cross‐linking,
and
interaction,
were
applied
improve
ROL.
Heterogeneous
modification
aspartic
glutamic
acid
residues
on
surface
was
carried
out
by
1‐ethyl‐3‐(3‐dimethylaminopropyl)
carbodiimide
(EDC)
introduce
new
amine
groups
with
lower
pKb.
The
highest
yield
89%
achieved
for
octyl‐agarose,
producing
specific
activity
45
U/mg,
which
15
folds
higher
than
soluble
enzyme.
Improved
observed,
particular
those
derivatives
obtained
attachment
glyoxyl‐agarose
(Gx‐ROL)
aminated
(Gx‐NH
2
‐ROL)
retaining
28%–36%
their
initial
activities
after
24
h
incubation
at
60°C.
Immobilization
also
altered
co‐solvent
profile
immobilized
biocatalysts
varied
stabilities.
Furthermore,
utilization
preparations
fish
oil
hydrolysis
revealed
selective
release
cis‐5,8,11,14,17‐eicosapentaenoic
(EPA)
cis‐4,7,10,13,16,19‐docosahexaenoic
(DHA)
favor
EPA.
EPA/DHA
33
observed
hydrophobically
octyl‐sepharose.
Frontiers in Chemistry,
Journal Year:
2022,
Volume and Issue:
10
Published: Feb. 28, 2022
Non-canonical
amino
acids
(ncAAs)
have
been
utilized
as
an
invaluable
tool
for
modulating
the
active
site
of
enzymes,
probing
complex
enzyme
mechanisms,
improving
catalytic
activity,
and
designing
new
to
nature
enzymes.
Here,
we
report
site-specific
incorporation
p
-benzoyl
phenylalanine
(
BpA)
engineer
R
)-amine
transaminase
previously
created
from
d
-amino
acid
aminotransferase
scaffold.
Replacement
single
Phe88
residue
at
with
BpA
exhibits
a
significant
15-fold
8-fold
enhancement
in
activity
1-phenylpropan-1-amine
benzaldehyde,
respectively.
Reshaping
enzyme’s
afforded
another
variant
F86A/F88
BpA,
30%
higher
thermostability
55°C
without
affecting
parent
activity.
Moreover,
various
racemic
amines
were
successfully
resolved
by
variants
into
S
)-amines
excellent
conversions
(∼50%)
enantiomeric
excess
(>99%)
using
pyruvate
acceptor.
Additionally,
kinetic
resolution
was
performed
benzaldehyde
acceptor,
which
is
cheaper
than
pyruvate.
Our
results
highlight
utility
ncAAs
enzymes
enhanced
functionality
beyond
limit
20
canonical
acids.
