Chemical Synthesis of Human Proteoforms and Application in Biomedicine
ACS Central Science,
Год журнала:
2024,
Номер
10(8), С. 1442 - 1459
Опубликована: Июль 22, 2024
Limited
understanding
of
human
proteoforms
with
complex
posttranslational
modifications
and
the
underlying
mechanisms
poses
a
major
obstacle
to
research
on
health
disease.
This
Outlook
discusses
opportunities
challenges
Язык: Английский
The Emerging Role of the Histone H2AK13/15 Ubiquitination: Mechanisms of Writing, Reading, and Erasing in DNA Damage Repair and Disease
Cells,
Год журнала:
2025,
Номер
14(4), С. 307 - 307
Опубликована: Фев. 18, 2025
Histone
modifications
serve
as
molecular
switches
controlling
critical
cellular
processes.
The
ubiquitination
of
histone
H2A
at
lysines
13
and
15
(H2AK13/15ub)
is
a
crucial
epigenetic
modification
that
coordinates
DNA
repair
genome
stability
during
the
damage
response
(DDR).
This
mark
dynamically
regulated
by
three
functional
protein
groups:
"writer"
enzymes
(e.g.,
E3
ubiquitin
ligase
RNF168
catalyzes
H2AK13/15ub
formation),
"reader"
proteins
(including
53BP1
BRCA1-BARD1
recognize
to
guide
repair),
"eraser"
deubiquitinases
(such
USP3
USP16
remove
modification).
Dysregulation
precisely
coordinated
network
strongly
associated
with
various
diseases,
including
RIDDLE
syndrome,
neurodegenerative
disorders,
immune
deficiencies,
breast
cancer.
review
systematically
analyzes
dynamic
regulation
in
DDR
explores
its
therapeutic
potential
for
disease
intervention.
Язык: Английский
Advances in the chemical synthesis of human proteoforms
Science China Life Sciences,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 8, 2025
Язык: Английский
Examining the Role of Threonine Phosphorylation in Ubiquitin’s Function Using Chemical Protein Synthesis
JACS Au,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 21, 2025
Язык: Английский
Mechanism of USP21 autoinhibition and histone H2AK119 deubiquitination
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 21, 2025
Abstract
Monoubiquitinated
histone
H2A
lysine
119
(H2AK119ub)
is
a
signature
modification
associated
with
transcriptional
silencing
and
heterochromatin
formation.
Ubiquitin-specific
protease
21
(USP21),
one
of
four
major
deubiquitinating
enzymes
(DUBs)
that
target
H2AK119ub,
plays
critical
roles
in
diverse
cellular
processes
1–4
.
The
molecular
mechanisms
by
which
USP21
specifically
deubiquitinates
H2AK119ub
regulated
unknown.
contains
C-terminal
USP
catalytic
domain,
preceded
an
N-terminal
intrinsically
disordered
region
(IDR).
We
determined
the
cryo-EM
structure
domain
bound
to
nucleosome,
reveals
recognition
mode
differs
from
two
other
H2AK119-specific
DUBs,
Polycomb
repressive
complex
5
USP16
6
unexpectedly
discovered
(IDR)
inhibits
enzyme’s
activity.
Using
AlphaFold-Multimer
perform
virtual
screen
interactors,
we
identified
kinases
phosphorylate
IDR
thereby
relieve
autoinhibition.
Modeling
using
AlphaFold3
suggests
structural
model
explaining
mechanism
AlphaFold
analysis
ubiquitin-specific
proteases
phosphorylation-regulated
autoinhibition
may
be
feature
multiple
enzymes.
These
findings
shed
light
on
H2AK119
deubiquitination
reveal
novel
phosphorylation-dependent
DUB
autoregulation.
Язык: Английский
Structure of the poxvirus core
Nature Structural & Molecular Biology,
Год журнала:
2024,
Номер
31(7), С. 1001 - 1003
Опубликована: Июнь 18, 2024
Язык: Английский
Development and applications of enzymatic peptide and protein ligation
Journal of Peptide Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 21, 2024
Chemical
synthesis
of
complex
peptides
and
proteins
continues
to
play
increasingly
important
roles
in
industry
academia,
where
strategies
for
covalent
ligation
two
or
more
peptide
fragments
produce
longer
convergent
manners
have
become
critical.
In
recent
decades,
efficient
site‐selective
mediated
by
exploiting
the
biocatalytic
capacity
nature's
diverse
toolkit
(i.e.,
enzymes)
been
widely
recognized
as
a
powerful
extension
existing
chemical
strategies.
this
review,
we
present
chronological
overview
development
proteases,
transpeptidases,
transglutaminases,
ubiquitin
ligases.
We
survey
different
properties
between
reactions
various
enzymes,
including
selectivity
efficiency
reaction,
“scar”
left
product,
type
amide
bond
formed
(natural
isopeptide),
synthetic
availability
reactants,
whether
enzymes
are
orthogonal
another.
This
review
also
describes
how
inherent
specificity
these
can
be
exploited
protein
ligation.
Язык: Английский