Prokaryotic
Argonaute
proteins
(pAgos)
from
the
long-A
clade
are
stand-alone
immune
systems
that
use
small
interfering
DNA
(siDNA)
guides
to
recognize
and
cleave
invading
plasmid
virus
DNA.
Certain
pAgos
co-encoded
with
accessory
unknown
functions.
Here,
we
show
cyanobacterial
act
in
conjunction
Argonaute-associated
Cas4
family
enzyme
1
(ACE1).
Structural
biochemical
analyses
reveal
ACE1-associated
mediate
siDNA-guided
interference,
akin
pAgos.
ACE1
is
structurally
homologous
nuclease
domain
of
bacterial
repair
complexes
acts
as
a
single-stranded
endonuclease
processes
siDNA
guides.
pAgo
form
heterodimeric
pAgo-ACE1
(APACE1)
complex,
which
modulates
activity.
Although
alone
interfere
plasmids
bacteriophages,
interference
boosted
when
co-expressed.
Our
study
reveals
pAgo-mediated
immunity
enhanced
by
broadens
our
mechanistic
understanding
how
Structural
comparison
reveals
remote
homology
that
often
fails
to
be
detected
by
sequence
comparison.
The
DALI
web
server
(http://ekhidna2.biocenter.helsinki.fi/dali)
is
a
platform
for
structural
analysis
provides
database
searches
and
interactive
visualization,
including
alignments
annotated
with
secondary
structure,
protein
families
logos,
3D
structure
superimposition
supported
color-coded
conservation.
Here,
we
are
using
mine
the
AlphaFold
Database
version
1,
which
increased
coverage
of
20%.
We
found
100
homologous
relationships
hitherto
unreported
in
current
reference
domains,
Pfam
35.0.
In
particular,
linked
35
domains
unknown
function
(DUFs)
previously
characterized
families,
generating
functional
hypothesis
can
explored
downstream
biology
studies.
Other
findings
include
gene
fusions,
tandem
duplications,
adjustments
domain
boundaries.
evidence
browsed
interactively
through
live
examples
on
DALI's
website.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Сен. 27, 2023
Abstract
Adapted
plant
pathogens
from
various
microbial
kingdoms
produce
hundreds
of
unrelated
small
secreted
proteins
(SSPs)
with
elusive
roles.
Here,
we
used
AlphaFold-Multimer
(AFM)
to
screen
1879
SSPs
seven
tomato
for
interacting
six
defence-related
hydrolases
tomato.
This
11,274
protein
pairs
identified
15
non-annotated
that
are
predicted
obstruct
the
active
site
chitinases
and
proteases
an
intrinsic
fold.
Four
were
experimentally
verified
be
inhibitors
pathogenesis-related
subtilase
P69B,
including
extracellular
protein-36
(Ecp36)
secreted-into-xylem-15
(Six15)
fungal
Cladosporium
fulvum
Fusarium
oxysporum
,
respectively.
Together
a
P69B
inhibitor
bacterial
pathogen
Xanthomonas
perforans
Kazal-like
oomycete
Phytophthora
infestans
emerges
as
effector
hub
targeted
by
different
kingdoms,
consistent
diversification
orthologs
paralogs.
study
demonstrates
power
artificial
intelligence
predict
cross-kingdom
interactions
at
plant-pathogen
interface.
Abstract
Motivation
Tools
for
pairwise
alignments
between
3D
structures
of
proteins
are
fundamental
importance
structural
biology
and
bioinformatics,
enabling
visual
exploration
evolutionary
functional
relationships.
However,
the
absence
a
user-friendly,
browser-based
tool
creating
visualizing
them
at
both
1D
sequence
levels
makes
this
process
unnecessarily
cumbersome.
Results
We
introduce
novel
structure
alignment
(rcsb.org/alignment)
that
seamlessly
integrates
into
RCSB
Protein
Data
Bank
(RCSB
PDB)
research-focused
RCSB.org
web
portal.
Our
its
underlying
application
programming
interface
(alignment.rcsb.org)
empowers
users
to
align
several
protein
chains
with
reference
by
providing
access
established
algorithms
(FATCAT,
CE,
TM-align,
or
Smith–Waterman
3D).
The
user-friendly
simplifies
parameter
setup
input
selection.
Within
seconds,
our
enables
visualization
results
in
(1D)
(3D)
perspectives
through
PDB
Sequence
Annotations
viewer
Mol*
viewer,
respectively.
Users
can
effortlessly
compare
deposited
archive
alongside
more
than
million
incorporated
Computed
Structure
Models
coming
from
ModelArchive
AlphaFold
DB.
Moreover,
be
used
custom
data
link/URL
uploading
atomic
coordinate
files
directly.
Importantly,
bookmarked
shared
collaborators.
By
bridging
gap
proteins,
facilitates
deeper
understanding
complex
relationships
among
comprehensive
analyses.
Availability
implementation
is
part
portal
available
rcsb.org/alignment.
Programmatic
via
alignment.rcsb.org.
Frontend
code
has
been
published
github.com/rcsb/rcsb-pecos-app.
Visualization
powered
open-source
(github.com/molstar/molstar
github.com/molstar/rcsb-molstar)
plus
Viewer
(github.com/rcsb/rcsb-saguaro-3d).
Journal of Hazardous Materials,
Год журнала:
2025,
Номер
487, С. 137177 - 137177
Опубликована: Янв. 10, 2025
Enzymatic
degradation
of
plastic
pollution
offers
a
promising
environmentally
friendly
waste
management
strategy,
however,
suitable
biocatalysts
must
be
screened
and
developed.
Traditional
screening
methods
using
soluble
or
solubilised
polymers
do
not
necessarily
identify
enzymes
that
are
effective
against
solid
crystalline
polymers.
This
study
presents
simple,
time-saving
cost-effective
method
for
identifying
microorganisms
capable
degrading
polymeric
films.
The
was
tested
on
polycaprolactone
(PCL),
polyethylene
terephthalate
(PET),
polylactate
(PLA)
polyhydroxybutyrate/polyhydroxyvalerate
(PHB/PHV)
It
involves
two
steps:
first,
PCL
diol
(PCLD)-degrading
agar
plates,
second,
testing
these
polyester
Using
this
method,
over
100
PCLD-degrading
27
E.
coli
clones
carrying
genomic
metagenomic
DNA
fragments
have
been
isolated.
In
addition,
recombinant
cutinases
from
Streptomyces
scabiei
Thermobifida
fusca
tested.
Approximately
66
%
the
forming
halos
PCLD
plates
hydrolysed
6
-
biaxially
oriented
PET
film.
five
PLA-
four
PHB/PHV-degrading
esterases
identified.
proposed
is
detecting
both
wild-type
microorganisms,
as
well
in
vitro
transcription-translation
reactions.
Screening
thermostable
thermophilic
enzymes,
including
those
resistant
to
organic
solvents
environmental
inhibitors,
also
easily
implemented.
Nature,
Год журнала:
2023,
Номер
626(7997), С. 186 - 193
Опубликована: Дек. 14, 2023
Abstract
The
long
interspersed
element-1
(LINE-1,
hereafter
L1)
retrotransposon
has
generated
nearly
one-third
of
the
human
genome
and
serves
as
an
active
source
genetic
diversity
disease
1
.
L1
spreads
through
a
mechanism
termed
target-primed
reverse
transcription,
in
which
encoded
enzyme
(ORF2p)
nicks
target
DNA
to
prime
transcription
its
own
or
non-self
RNAs
2
Here
we
purified
full-length
ORF2p
biochemically
reconstituted
robust
with
template
RNA
target-site
DNA.
We
report
cryo-electron
microscopy
structures
complete
bound
structured
initiating
cDNA
synthesis.
polyadenosine
tract
is
recognized
sequence-specific
manner
by
five
distinct
domains.
Among
them,
RNA-binding
domain
bends
backbone
allow
engagement
hairpin
stem
C-terminal
segment.
Moreover,
structure
biochemical
reconstitutions
demonstrate
unexpected
requirement:
relies
on
upstream
single-stranded
position
adjacent
duplex
endonuclease
site
for
nicking
longer
strand,
single
nick
generating
staggered
break.
Our
research
provides
insights
into
ongoing
transposition
informs
engineering
proteins
gene
therapy.
ACS Catalysis,
Год журнала:
2023,
Номер
14(1), С. 475 - 488
Опубликована: Дек. 21, 2023
Glycosyltransferases
are
effective
enzymes
for
glycosylating
natural
products
(NPs),
and
some
of
them
have
the
unusual
property
being
exceedingly
promiscuous
catalytically
toward
a
range
substrates.
UGT74AN3
is
plant
glycosyltransferase
identified
from
Catharanthus
roseus
in
our
previous
work.
In
this
study,
we
found
that
exhibits
high
substrate
promiscuity
78
acceptors
6
sugar
donors
also
N-/S-glycosylation
activity
simple
aromatic
compounds.
The
crystal
structures
complex
with
various
NPs
were
solved.
Sugar
donor
recognition
was
altered
by
structure-based
mutagenesis,
T145V
mutant
shifted
its
preference
UDP-Glc
to
UDP-Xyl.
Structural
analysis
reveals
spacious
U-shaped
hydrophobic
binding
pocket
accounts
UGT74AN3.
residues
E85
F193
might
serve
as
gatekeepers
control
binding.
addition,
rare
mode
discovered
structure
UGT74AN3,
process
flipping
charted
molecular
dynamics
simulations.
Moreover,
cost-effective
one-pot
system
coupling
AtSuSy,
sucrose
synthase,
established
situ
generating
recycling
UDP
glycosylate
NPs.
Our
study
structural
basis
underlying
provides
an
efficient
economical
enzymatic
synthesis
strategy
producing
valuable
glycosides
drug
discovery.
Science,
Год журнала:
2024,
Номер
385(6706), С. 276 - 282
Опубликована: Июль 18, 2024
We
describe
an
approach
for
designing
high-affinity
small
molecule–binding
proteins
poised
downstream
sensing.
use
deep
learning–generated
pseudocycles
with
repeating
structural
units
surrounding
central
binding
pockets
widely
varying
shapes
that
depend
on
the
geometry
and
number
of
repeat
units.
dock
molecules
interest
into
most
shape
complementary
these
pseudocycles,
design
interaction
surfaces
high
affinity,
experimentally
screen
to
identify
designs
highest
affinity.
obtain
binders
four
diverse
molecules,
including
polar
flexible
methotrexate
thyroxine.
Taking
advantage
modular
structure
pockets,
we
construct
chemically
induced
dimerization
systems
low-noise
nanopore
sensors
by
splitting
domains
reassemble
upon
ligand
addition.