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Oxidoreductase
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PDB id
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1ys4
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* Residue conservation analysis
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Enzyme class:
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E.C.1.2.1.11
- Aspartate-semialdehyde dehydrogenase.
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Pathway:
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Lysine biosynthesis (early stages)
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Reaction:
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L-aspartate 4-semialdehyde + phosphate + NADP+ = L-4-aspartyl phosphate + NADPH
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L-aspartate 4-semialdehyde
Bound ligand (Het Group name = )
matches with 50.00% similarity
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phosphate
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NADP(+)
Bound ligand (Het Group name = )
corresponds exactly
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=
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L-4-aspartyl phosphate
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NADPH
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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Gene Ontology (GO) functional annotation
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Cellular component
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cytoplasm
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1 term
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Biological process
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oxidation-reduction process
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9 terms
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Biochemical function
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nucleotide binding
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8 terms
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DOI no:
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J Mol Biol
353:1055-1068
(2005)
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PubMed id:
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A new branch in the family: structure of aspartate-beta-semialdehyde dehydrogenase from Methanococcus jannaschii.
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C.R.Faehnle,
J.F.Ohren,
R.E.Viola.
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ABSTRACT
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The structure of aspartate-beta-semialdehyde dehydrogenase (ASADH) from
Methanococcus jannaschii has been determined to 2.3 angstroms resolution using
multiwavelength anomalous diffraction (MAD) phasing of a
selenomethionine-substituted derivative to define a new branch in the family of
ASADHs. This new structure has a similar overall fold and domain organization
despite less than 10% conserved sequence identity with the bacterial enzymes.
However, the entire repertoire of functionally important active site amino acid
residues is conserved, suggesting an identical catalytic mechanism but with
lower catalytic efficiency. A new coenzyme-binding conformation and dual
NAD/NADP coenzyme specificity further distinguish this archaeal branch from the
bacterial ASADHs. Several structural differences are proposed to account for the
dramatically enhanced thermostability of this archaeal enzyme. Finally, the
intersubunit communication channel connecting the active sites in the bacterial
enzyme dimer has been disrupted in the archaeal ASADHs by amino acid changes
that likely prevent the alternating sites reactivity previously proposed for the
bacterial ASADHs.
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Selected figure(s)
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Figure 3.
Figure 3. Topology maps comparing the secondary structural
arrangements in the catalytic and dimerization interface regions
of mjASADH with that of a representative bacterial enzyme,
vcASADH. Maps were created by using the TopDraw program.50
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Figure 7.
Figure 7. Overlay of the dimerization interfaces for
mjASADH and vcASADH. The subunit interface of vcASADH (white) is
bridged by a hydrogen-bonded network (broken lines) that
connected the active sites of each subunit and is stabilized by
p-stacking interactions (dotted lines). In the mjASADH interface
(green) replacement of tyrosine with methionine (M183)
interrupts the hydrogen-bonding network, and replacement of
phenylalanine with threonine (T328) disrupts the p-stacking
stabilization.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2005,
353,
1055-1068)
copyright 2005.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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B.T.Arachea,
X.Liu,
A.G.Pavlovsky,
and
R.E.Viola
(2010).
Expansion of the aspartate beta-semialdehyde dehydrogenase family: the first structure of a fungal ortholog.
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Acta Crystallogr D Biol Crystallogr, 66,
205-212.
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A.Singh,
H.R.Kushwaha,
and
P.Sharma
(2008).
Molecular modelling and comparative structural account of aspartyl beta-semialdehyde dehydrogenase of Mycobacterium tuberculosis (H37Rv).
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J Mol Model, 14,
249-263.
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R.E.Viola,
X.Liu,
J.F.Ohren,
and
C.R.Faehnle
(2008).
The structure of a redundant enzyme: a second isoform of aspartate beta-semialdehyde dehydrogenase in Vibrio cholerae.
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Acta Crystallogr D Biol Crystallogr, 64,
321-330.
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PDB codes:
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R.Vyas,
V.Kumar,
S.Panjikar,
S.Karthikeyan,
K.V.Kishan,
R.Tewari,
and
M.S.Weiss
(2008).
Purification, crystallization and preliminary X-ray diffraction analysis of aspartate semialdehyde dehydrogenase (Rv3708c) from Mycobacterium tuberculosis.
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Acta Crystallogr Sect F Struct Biol Cryst Commun, 64,
167-170.
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B.Alber,
M.Olinger,
A.Rieder,
D.Kockelkorn,
B.Jobst,
M.Hügler,
and
G.Fuchs
(2006).
Malonyl-coenzyme A reductase in the modified 3-hydroxypropionate cycle for autotrophic carbon fixation in archaeal Metallosphaera and Sulfolobus spp.
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J Bacteriol, 188,
8551-8559.
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C.R.Faehnle,
J.Le Coq,
X.Liu,
and
R.E.Viola
(2006).
Examination of key intermediates in the catalytic cycle of aspartate-beta-semialdehyde dehydrogenase from a gram-positive infectious bacteria.
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J Biol Chem, 281,
31031-31040.
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PDB codes:
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C.R.Faehnle,
X.Liu,
A.Pavlovsky,
and
R.E.Viola
(2006).
The initial step in the archaeal aspartate biosynthetic pathway catalyzed by a monofunctional aspartokinase.
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Acta Crystallogr Sect F Struct Biol Cryst Commun, 62,
962-966.
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
