Abstract
The
easiest
and
often
most
useful
way
to
work
with
experimentally
determined
or
computationally
predicted
structures
of
biomolecules
is
by
viewing
their
three‐dimensional
(3D)
shapes
using
a
molecular
visualization
tool.
Mol*
was
collaboratively
developed
RCSB
Protein
Data
Bank
(RCSB
PDB,
RCSB.org
)
in
Europe
(PDBe,
PDBe.org
as
an
open‐source,
web‐based,
3D
software
suite
for
examination
analyses
biostructures.
It
capable
displaying
atomic
coordinates
related
experimental
data
biomolecular
together
variety
annotations,
facilitating
basic
applied
research,
training,
education,
information
dissemination.
Across
,
the
PDB
research‐focused
web
portal,
has
been
implemented
support
single‐mouse‐click
atomic‐level
(e.g.,
proteins,
nucleic
acids,
carbohydrates)
bound
cofactors,
small‐molecule
ligands,
ions,
water
molecules,
other
macromolecules.
can
seamlessly
display
from
various
sources,
allowing
structure
interrogation,
superimposition,
comparison.
Using
influenza
A
H5N1
virus
topical
case
study
important
pathogen,
we
exemplify
how
embedded
within
tools—allowing
users
view
polymer
sequence
structure‐based
annotations
integrated
trusted
bioinformatics
resources,
assess
patterns
trends
groups
structures,
any
size
compositional
complexity.
In
addition
being
linked
every
biostructure
Computed
Structure
Model
made
available
at
Standalone
freely
visualizing
multi‐scale
rcsb.org/3d-view
.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 18, 2025
Abstract
The
Flaviviridae
are
a
family
of
non-segmented
positive-sense
enveloped
RNA
viruses
containing
significant
pathogens
including
hepatitis
C
virus
and
yellow
fever
virus.
Recent
large-scale
metagenomic
surveys
have
identified
many
diverse
related
to
classical
orthoflaviviruses
pestiviruses
but
quite
different
genome
lengths
configurations,
with
hugely
expanded
host
range
that
spans
multiple
animal
phyla,
molluscs,
cnidarians
stramenopiles,,
plants.
Grouping
RNA-directed
polymerase
(RdRP)
hallmark
gene
sequences
flavivirus
‘flavi-like’
into
four
divergent
clades
lineages
within
them
was
congruent
helicase
phylogeny,
PPHMM
profile
comparisons,
comparison
RdRP
protein
structure
predicted
by
AlphFold2.
These
results
support
their
classification
the
established
order,
Amarillovirales
,
in
three
families
(
Flaviviridae,
Pestiviridae
Hepaciviridae
),
14
genera.
This
taxonomic
framework
informed
evolutionary
relationships
provides
stable
reference
from
which
major
re-organisational
events
can
be
understood.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 20, 2025
Enterococcus
faecalis
,
a
gut
commensal,
is
leading
cause
of
opportunistic
infections.
Its
virulence
linked
to
its
ability
thrive
in
hostile
environments,
which
includes
host-imposed
metal
starvation.
We
recently
showed
that
E.
evades
iron
starvation
using
five
dedicated
transporters
collectively
scavenge
from
host
tissues
and
other
iron-deprived
conditions.
Interestingly,
heme,
the
most
abundant
source
human
body,
supported
growth
strain
lacking
all
(Δ5Fe).
To
release
many
bacterial
pathogens
utilize
heme
oxygenase
enzymes
degrade
porphyrin
coordinates
ion
heme.
Although
lacks
these
enzymes,
bioinformatics
revealed
potential
ortholog
anaerobic
heme-degrading
enzyme
anaerobilin
synthase,
found
Escherichia
coli
few
Gram-negative
bacteria.
Here,
we
demonstrated
deletion
OG1RF_RS05575
(ΔRS05575)
or
Δ5Fe
background
(Δ5FeΔRS05575)
led
intracellular
accumulation
hypersensitivity
under
conditions,
suggesting
RS05575
encodes
an
first
kind
described
Gram-
positive
Additionally,
either
alone
background,
impaired
colonization
mouse
gastrointestinal
tract
peritonitis
rabbit
infective
endocarditis
models.
These
results
reveal
responsible
for
degradation
identify
this
relatively
new
class
as
novel
factor
pathogenesis.
Findings
study
are
likely
have
broad
implications,
homologues
Gram-positive
facultative
anaerobes.
Heme
important
nutrient
pathogens,
mainly
serve
during
infection.
While
bacteria
known
called
oxygenases,
family
has
been
report
description
by
bacterium,
pathogen
link
activity
their
colonize
infect
host.
also
show
anaerobes,
implying
conditions
may
be
overlooked
fitness
pathogens.
Journal of Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 22, 2025
We
optimized
our
highly
potent
and
cell-active
chemical
probe
for
phosphatidylinositol-3-phosphate
5-kinase
(PIKfyve),
SGC-PIKFYVE-1,
resulting
in
compounds
with
improved
potency
demonstrated
vivo
stability.
Use
of
an
in-cell,
kinome-wide
selectivity
panel
allowed
confirmation
excellent
in-cell
lead
compound,
40,
another
promising
analogue,
46.
Evaluation
the
pharmacokinetic
(PK)
profiles
these
two
revealed
that
both
are
well
tolerated
systemically
orally
bioavailable.
Coupled
its
subnanomolar
cellular
impressive
cells,
long
half-life
40
makes
it
ideal
candidate
evaluation
consequences
PIKfyve
inhibition
vivo.
has
been
investigated
clinically
indications
including
rheumatoid
arthritis,
Crohn's
disease,
COVID-19,
ALS
using
a
single
compound
(apilimod),
supporting
development
orthogonal
inhibitors
Genome Biology and Evolution,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 24, 2025
Abstract
Homology
is
a
key
concept
underpinning
the
comparison
of
sequences
across
organisms.
Sequence-level
homology
based
on
statistical
framework
optimized
over
decades
work.
Recently,
computational
protein
structure
prediction
has
enabled
large-scale
inference
beyond
limits
accurate
sequence
alignment.
In
this
regime
it
possible
to
observe
nearly
identical
structures
lacking
detectable
similarity.
absence
robust
for
comparison,
largely
assumed
similar
are
homologous.
However,
conceivable
that
matching
could
arise
through
convergent
evolution,
resulting
in
analogous
proteins
without
shared
ancestry.
Large
databases
predicted
offer
means
determining
whether
analogs
present
among
matches.
Here,
I
find
small
subset
(∼2.6%)
Foldseek
clusters
lack
sequence-level
support
homology,
including
∼1%
strong
matches
with
TM-score
≥
0.5.
This
result
by
itself
does
not
imply
these
pairs
non-homologous,
since
their
have
diverged
recognition.
Yet,
enriched
repeats
induce
spurious
Some
structural
underpinned
tandem
both
structures.
show
many
repeat
units
genealogies
inconsistent
corresponding
sharing
common
ancestor,
implying
highly
rather
than
suggests
caution
warranted
when
inferring
from
resemblance
alone
homology.
Life,
Год журнала:
2025,
Номер
15(2), С. 192 - 192
Опубликована: Янв. 28, 2025
Chagas
disease,
caused
by
the
protozoan
Trypanosoma
cruzi,
represents
a
significant
public
health
challenge,
particularly
in
Latin
America’s
endemic
regions.
The
limited
efficacy
and
frequent
adverse
effects
of
current
treatments
underscore
need
for
novel
therapeutic
options.
This
research
explores
marine
natural
compounds
as
potential
candidates
disease
treatment
using
virtual
screening
silico
evaluation
methods.
Techniques
such
molecular
docking,
drug-likeness
evaluation,
pharmacokinetic
analysis
were
employed
to
identify
promising
anti-parasitic
compounds.
Among
candidates,
chandrananimycin
A,
venezueline
dispacamide
demonstrated
high
binding
affinities
key
targets
T.
cruzi
alongside
favorable
docking
scores
compliance
with
essential
criteria.
Pharmacokinetic
profiling
further
supported
their
potential,
revealing
desirable
properties
like
effective
absorption
minimal
toxicity.
These
findings
promise
marine-derived
valuable
source
new
drugs,
emphasizing
vitro
vivo
investigations
elucidate
mechanisms
optimize
development
viable
disease.
International Journal of Biological Macromolecules,
Год журнала:
2025,
Номер
unknown, С. 140575 - 140575
Опубликована: Фев. 1, 2025
Arabinoxylan
is
a
prevalent
hemicellulose
type,
notably
heterogeneous
and
resistant
to
biodegradation.
Arabinofuranosidases
(Abfs)
remove
arabinofuranosyl
decorations
of
arabinoxylan,
thus
enabling
hydrolysis
by
xylanases.
However,
variety
Abf
xylanase
specificities
have
emerged
in
recent
years,
necessitating
deeper
understanding
their
role
biomass
degradation.
This
work
investigates
the
biochemical
features
TtAbf43
from
Thermothelomyces
thermophila,
which
specifically
removes
O-3-linked
arabinofuranose
moieties
di-substituted
xylopyranoses.
The
enzyme
also
exhibited
secondary
hydrolytic
activity
on
o-nitrophenyl-β-d-xylopyranoside
arabinan.
pretreated
wheat
corn
bran
substrates
was
assessed
using
AnAbf51,
two
enzymes
with
distinct
catalytic
specificities.
Abfs
enhanced
performance
endo-xylanases
TmXyn10
AnXyn11,
promoting
release
xylo-oligomers,
while
xylanases,
turn,
stimulated
arabinose
Abfs.
Additionally,
facilitated
endo-
exo-activities
bifunctional
xylobiohydrolase/glucuronoxylanase
TtXyn30A
for
xylobiose
short
aldouronic
acids
biomass.
AnAbf51
acted
synergy
acetyl
xylan
esterase
OCE6
exo-deacetylase
TtCE16B
debranching
enzymatically
derived
oligomers
lignocellulose,
whereas
remained
unaffected
esterases.
These
diverse
synergistic
relationships
among
different
hemicellulases
could
assist
development
new
enzymatic
approaches
efficient
valorization.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 9, 2025
Abstract
As
organisms
adapt
to
environmental
changes,
natural
selection
modifies
the
frequency
of
non-neutral
alleles.
For
beneficial
mutations,
outcome
this
process
may
be
a
selective
sweep,
in
which
an
allele
rapidly
increases
and
perhaps
reaches
fixation
within
population.
Selective
sweeps
have
well-studied
effects
on
patterns
local
genetic
variation
panmictic
populations,
but
much
less
is
known
about
dynamics
continuous
space.
In
particular,
because
limited
movement
across
landscape
leads
unique
population
structure,
spatial
influence
trajectory
selected
mutations.
Here,
we
use
forward-in-time,
individual-based
simulations
space
study
impact
mutations
as
they
sweep
through
show
that
changes
joint
distribution
geographic
range
occupied
by
focal
demonstrate
signal
can
used
identify
sweeps.
We
then
leverage
in-progress
malaria
vector
Anopheles
gambiae
,
species
under
strong
pressure
from
control
measures.
By
considering
space,
multiple
previously
undescribed
variants
with
potential
phenotypic
consequences,
including
im-pacting
IR-associated
genes
altering
protein
structure
properties.
Our
results
novel
for
detecting
data
implications
genomic
surveillance
understanding
variation.