FEBS Journal,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 3, 2025
NrdR
is
a
bacterial
transcriptional
repressor
consisting
of
zinc
(Zn)‐ribbon
domain
followed
by
an
ATP‐cone
domain.
Understanding
its
mechanism
action
could
aid
the
design
novel
antibacterials.
binds
specifically
to
two
“NrdR
boxes”
upstream
ribonucleotide
reductase
operons,
which
Escherichia
coli
has
three:
nrdHIEF,
nrdDG
and
nrdAB,
in
last
we
identified
new
box.
We
show
that
E.
(EcoNrdR)
similar
binding
strength
all
three
sites
when
loaded
with
ATP
plus
deoxyadenosine
triphosphate
(dATP)
or
equivalent
diphosphate
combinations.
No
other
combination
adenine
nucleotides
promotes
DNA.
present
crystal
structures
EcoNrdR–ATP–dATP
EcoNrdR–ADP–dATP,
are
first
high‐resolution
NrdR.
have
also
determined
cryo‐electron
microscopy
DNA‐bound
filaments
EcoNrdR–ATP.
Tetrameric
forms
EcoNrdR
involve
alternating
interactions
between
pairs
Zn‐ribbon
domains
ATP‐cones.
The
reveal
considerable
flexibility
relative
orientation
ATP‐cones
vs
domains.
structure
shows
significant
conformational
rearrangements
Zn‐ribbons
accompany
DNA
while
retain
same
orientation.
In
contrast,
ATP‐loaded
sequester
DNA‐binding
residues
such
they
unable
bind
Our
results,
previous
structural
biochemical
study,
point
highly
flexible
that,
correct
nucleotides,
adapt
optimal
promoter‐binding
conformation.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Sept. 21, 2023
Abstract
Recent
advances
in
AI-based
protein
structure
modeling
have
yielded
remarkable
progress
predicting
structures.
Since
structures
are
constrained
by
their
biological
function,
geometry
tends
to
evolve
more
slowly
than
the
underlying
amino
acids
sequences.
This
feature
of
could
principle
be
used
reconstruct
phylogenetic
trees
over
longer
evolutionary
timescales
sequence-based
approaches,
but
until
now
a
reliable
structure-based
tree
building
method
has
been
elusive.
Here,
we
demonstrate
that
structure-informed
phylogenies
can
outperform
sequence-only
ones
not
only
for
distantly
related
proteins
also,
remarkably,
closely
ones.
is
achieved
inferring
from
using
local
structural
alphabet,
an
approach
robust
conformational
changes
confound
traditional
distance
measures.
As
illustration,
decipher
diversification
particularly
challenging
family:
fast-evolving
RRNPPA
quorum
sensing
receptors
enabling
gram-positive
bacteria,
plasmids
and
bacteriophages
communicate
coordinate
key
behaviors
such
as
sporulation,
virulence,
antibiotic
resistance,
conjugation
or
phage
lysis/lysogeny
decision.
The
advent
high-accuracy
phylogenetics
enables
myriad
applications
across
biology,
uncovering
deeper
relationships,
elucidating
unknown
functions,
refining
design
bioengineered
molecules.
Plant and Cell Physiology,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 22, 2024
Research
on
chlorophyll
degradation
has
progressed
significantly
in
recent
decades.
In
the
1990s,
structure
of
linear
tetrapyrrole,
which
is
unambiguously
a
product,
was
determined.
From
2000s
until
2010s,
major
enzymes
involved
were
identified,
and
pheophorbide
oxygenase/phyllobilin
pathway
established.
This
encompasses
several
steps:
(1)
initial
conversion
b
to
7-hydroxymethyl
a;
(2)
(3)
dechelation
pheophytin
(4)
dephytylation
(5)
opening
macrocycle
yield
red
catabolite;
(6)
catabolite
phyllobilins.
converts
potentially
harmful
into
safe
molecules
phyllobilins,
are
stored
central
vacuole
terrestrial
plants.
The
expression
chlorophyll-degrading
mediated
by
various
transcription
factors
influenced
light
conditions,
stress,
plant
hormones.
Chlorophyll
differently
regulated
different
organs
developmental
stages
initiation
induces
further
enzymes,
resulting
acceleration
degradation.
initially
considered
last
reaction
senescence;
however,
plays
crucial
roles
enhancing
senescence,
degrading
chlorophyll-protein
complexes,
forming
photosystem
II,
maintaining
seed
quality.
Therefore,
controlling
important
agricultural
applications.
Molecular Microbiology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 18, 2025
ABSTRACT
NrdR
is
a
universal
transcriptional
repressor
of
bacterial
genes
coding
for
ribonucleotide
reductases
(RNRs),
essential
enzymes
that
provide
DNA
building
blocks
in
all
living
cells.
Despite
its
prevalence,
the
mechanism
has
been
scarcely
studied.
We
report
biochemical,
biophysical,
and
bioinformatical
characterization
binding
sites
from
two
major
pathogens
phylum
Bacillota
Listeria
monocytogenes
Streptococcus
pneumoniae
.
consists
Zn‐ribbon
domain
followed
by
an
ATP‐cone
domain.
show
it
forms
tetramers
bind
to
when
loaded
with
ATP
dATP,
but
if
only
ATP,
various
oligomeric
complexes
unable
DNA.
The
DNA‐binding
site
L.
pair
boxes
separated
15–16
bp,
whereas
S.
,
are
unusually
long
spacers
25–26
bp.
This
observation
triggered
comprehensive
study
four
NrdRs
Escherichia
coli
Streptomyces
coelicolor
series
dsDNA
fragments
where
were
12–27
vitro
results
confirmed
vivo
E.
revealed
binds
most
efficiently
there
integer
number
turns
between
center
boxes.
facilitates
prediction
genomes
suggests
conserved
throughout
It
sheds
light
on
RNR
regulation
since
does
not
occur
eukaryotes,
opens
way
development
novel
antibiotics.
Molecular Cell,
Journal Year:
2017,
Volume and Issue:
66(2), P. 206 - 220.e9
Published: April 1, 2017
Cells
exposed
to
hypoxia
experience
replication
stress
but
do
not
accumulate
DNA
damage,
suggesting
sustained
replication.
Ribonucleotide
reductase
(RNR)
is
the
only
enzyme
capable
of
de
novo
synthesis
deoxyribonucleotide
triphosphates
(dNTPs).
However,
oxygen
an
essential
cofactor
for
mammalian
RNR
(RRM1/RRM2
and
RRM1/RRM2B),
leading
us
question
source
dNTPs
in
hypoxia.
Here,
we
show
that
RRM1/RRM2B
retaining
activity
therefore
favored
over
RRM1/RRM2
order
preserve
ongoing
avoid
accumulation
damage.
We
found
two
distinct
mechanisms
by
which
RRM2B
maintains
hypoxic
identified
responsible
residues
RRM2B.
The
importance
response
tumor
further
illustrated
correlation
its
expression
with
a
signature
patient
samples
roles
growth
radioresistance.
Our
data
provide
mechanistic
insight
into
biology,
highlighting
as
hypoxic-specific,
anti-cancer
therapeutic
target.
Critical Reviews in Biochemistry and Molecular Biology,
Journal Year:
2017,
Volume and Issue:
52(6), P. 674 - 695
Published: Sept. 13, 2017
Glycyl
radical
enzymes
(GREs)
are
important
biological
catalysts
in
both
strict
and
facultative
anaerobes,
playing
key
roles
the
human
microbiota
environment.
GREs
contain
a
backbone
glycyl
that
is
post-translationally
installed,
enabling
radical-based
mechanisms.
function
several
metabolic
pathways
including
mixed
acid
fermentation,
ribonucleotide
reduction
anaerobic
breakdown
of
nutrient
choline
pollutant
toluene.
By
generating
substrate-based
species
within
active
site,
enable
C-C,
C-O
C-N
bond
breaking
formation
steps
otherwise
challenging
for
nonradical
enzymes.
Identification
previously
unknown
family
members
from
genomic
data
determination
structures
well-characterized
have
expanded
scope
GRE-catalyzed
reactions
as
well
defined
features
catalysis.
Here,
we
review
mechanisms
characterized
GREs,
classifying
into
five
categories.
We
consider
open
questions
about
each
GRE
classes
evaluate
tools
available
to
interrogate
uncharacterized
GREs.
Journal of Molecular Evolution,
Journal Year:
2016,
Volume and Issue:
82(1), P. 17 - 26
Published: Jan. 1, 2016
The
triosephosphate
isomerase
(TIM)
barrel
protein
fold
is
a
structurally
repetitive
architecture
that
present
in
approximately
10
%
of
all
enzymes.
It
generally
assumed
this
ubiquity
modern
proteomes
reflects
an
essential
historical
role
early
protein-mediated
metabolism.
Here,
we
provide
quantitative
and
comparative
analyses
to
support
several
hypotheses
about
the
importance
TIM
architecture.
An
information
theoretical
analysis
structures
supports
hypothesis
could
arise
more
easily
by
duplication
recombination
compared
other
mixed
α/β
structures.
We
show
enzymes
corresponding
most
taxonomically
broad
superfamilies
also
have
broadest
range
functions,
often
aided
metal
nucleotide-derived
cofactors
are
thought
reflect
earlier
stage
metabolic
evolution.
By
comparison
putatively
ancient
architectures,
find
functional
diversity
proteins
cannot
be
explained
simply
their
antiquity.
Instead,
breadth
functions
can
explained,
part,
incorporation
cofactors,
trend
does
not
appear
shared
general.
These
results
simple
functionally
general
may
arisen
evolution
biosynthesis
provided
ideal
scaffold
facilitate
transition
from
ribozymes,
peptides,
geochemical
catalysts