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The DDE recombinases: diverse roles in acquired and innate immunity.
[omenn syndrome]
The
RAG
proteins
required
for
V
(
D
)
J
recombination
of
immunoglobulin
and
T
-
cell
receptor
genes
in
the
acquired
immune
response
contain
a
magnesium
ion-binding
site
termed
a
DDE
site
,
composed
of
D
(
aspartic
acid
)
and
E
(
glutamic
acid
)
amino
acids
.
A
similar
DDE-like
magnesium
binding
site
also
is
present
in
transposases
,
retroviral
integrases
,
and
the
innate
antiviral
response
enzymes
RNAse
H
and
RNA-induced
silencing
complex
(
RISC
)
.
To
help
clinicians
understand
immunodeficiency
that
results
from
deficiencies
of
RAG
protein
functions
,
such
as
severe
combined
immunodeficiency
disorders
,
Omenn
syndrome
,
and
ataxia
telangiectasia
,
and
to
be
familiar
with
the
diverse
roles
of
other
DDE
enzymes
.
Literature
published
in
peer
-reviewed
journals
during
the
past
2
decades
that
identified
and
characterized
DDE
enzymes
,
including
RAG
proteins
,
RISC
and
RNA
silencing
,
RNAse
H
,
retroviral
integrases
,
transposases
,
and
a
putative
DDE
recombinase
required
for
herpes
virus
replication
,
was
selectively
reviewed
and
summarized
by
the
author
.
DDE
enzymes
play
a
critical
role
in
acquired
immunity
through
RAG-mediated
immunoglobulin
and
T
-
cell
receptor
V
(
D
)
J
recombination
in
innate
immunity
through
RISC
and
RNAse
H
.
Paradoxically
,
DDE
enzymes
are
critical
components
of
pathogen-
specific
enzymes
such
as
retroviral
integrase
and
other
pathogen-encoded
proteins
.
Because
of
their
critical
role
in
acquired
and
innate
immunity
,
the
DDE
recombinases
are
attractive
targets
for
novel
pharmacologic
therapies
.
Currently
,
retroviral
integrase
inhibitors
in
clinical
trial
for
human
immunodeficiency
virus
infection
appear
to
be
safe
and
effective
and
could
provide
a
paradigm
for
inactivating
DDE
sites
in
other
viral
pathogens
,
as
well
as
RAG
and
RISC
.
Diseases
Validation
Diseases presenting
"other pathogen-encoded proteins"
symptom
omenn syndrome
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