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Oxidoreductase
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PDB id
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1brm
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Contents |
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* Residue conservation analysis
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PDB id:
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Oxidoreductase
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Title:
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Aspartate beta-semialdehyde dehydrogenase from escherichia coli
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Structure:
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Aspartate-semialdehyde dehydrogenase. Chain: a, b, c. Synonym: asadh, asdh. Engineered: yes
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Source:
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Escherichia coli. Organism_taxid: 562. Gene: asd. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_cell_line: jm109.
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Biol. unit:
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Homo-Dimer (from PDB file)
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Resolution:
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2.50Å
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R-factor:
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0.225
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R-free:
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0.294
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Authors:
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A.T.Hadfield,G.Kryger,J.Ouyang,D.Ringe,G.A.Petsko,R.E.Viola
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Key ref:
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A.Hadfield
et al.
(1999).
Structure of aspartate-beta-semialdehyde dehydrogenase from Escherichia coli, a key enzyme in the aspartate family of amino acid biosynthesis.
J Mol Biol,
289,
991.
PubMed id:
DOI:
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Date:
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24-Aug-98
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Release date:
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22-Jun-99
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PROCHECK
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Headers
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References
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P0A9Q9
(DHAS_ECOLI) -
Aspartate-semialdehyde dehydrogenase
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Seq:
Struc:
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367 a.a.
356 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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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
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+
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phosphate
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+
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NADP(+)
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=
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L-4-aspartyl phosphate
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+
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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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10 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
289:991
(1999)
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PubMed id:
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| |
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Structure of aspartate-beta-semialdehyde dehydrogenase from Escherichia coli, a key enzyme in the aspartate family of amino acid biosynthesis.
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A.Hadfield,
G.Kryger,
J.Ouyang,
G.A.Petsko,
D.Ringe,
R.Viola.
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ABSTRACT
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Aspartate beta-semialdehyde dehydrogenase (ASADH) lies at the first branch point
in an essential aspartic biosynthetic pathway found in bacteria, fungi and the
higher plants. Mutations in the asd gene encoding for ASADH that produce an
inactive enzyme are lethal, which suggests that ASADH may be an effective target
for antibacterial, herbicidal and fungicidal agents.We have solved the crystal
structure of the Escherichia coli enzyme to 2.5 A resolution using single
isomorphous replacement and 3-fold non-crystallographic symmetry. Each monomer
has an N-terminal nucleotide-binding domain and a dimerisation domain. The
presence of an essential cysteine locates the active site in a cleft between the
two domains. The functional dimer has the appearance of a butterfly, with the
NADP-binding domains forming the wings and the dimerisation domain forming the
body.A histidine residue is identified as a likely acid/base catalyst in the
enzymic reaction. Other amino acids implicated in the enzymic activity by
mutagenesis are found in the active site region and define the substrate binding
pocket.
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Selected figure(s)
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Figure 4.
Figure 4. Comparison of the aspartate-b-semialdehyde dehydrogenase and glyceraldehyde-3-phosphate dehydrogen-
ase, which perform similar chemistry. (a) Structure-based sequence alignment of ASADH and GAPDH. Secondary struc-
ture elements are represented by cylinders (a-helix) and arrows (b-strands), above the sequence for ASADH and below
for GAPDH. The NAD(P)-binding fold fingerprint glycine residues and catalytic cysteine residues are boxed and similar
residues are shaded (Barton, 1993). (b) Stereo views showing C
a
traces of the superimposed structures of B. stearothermo-
philus GAPDH (grey) and E. coli ASADH (black). Numbering corresponds to ASADH sequence. (i) Dimerisation domain
(ii) NADP-binding domain. The Figure was prepared using MOLSCRIPT (Kraulis, 1991).
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Figure 5.
Figure 5. Cartoon representation of the active sites of
GAPDH (grey) and ASADH (black). A sulphate (shown
in grey) is observed in the GAPDH crystal structure and
is believed to indicate part of the substrate binding site.
The Figure was prepared using MOLSCRIPT (Kraulis,
1991).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1999,
289,
991-0)
copyright 1999.
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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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A.S.Evitt,
and
R.J.Cox
(2011).
Synthesis and evaluation of conformationally restricted inhibitors of aspartate semialdehyde dehydrogenase.
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Mol Biosyst, 7,
1564-1575.
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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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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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F.Fabiola,
A.Korostelev,
and
M.S.Chapman
(2006).
Bias in cross-validated free R factors: mitigation of the effects of non-crystallographic symmetry.
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Acta Crystallogr D Biol Crystallogr, 62,
227-238.
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S.Shafiani,
P.Sharma,
R.M.Vohra,
and
R.Tewari
(2005).
Cloning and characterization of aspartate-beta-semialdehyde dehydrogenase from Mycobacterium tuberculosis H37 Rv.
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J Appl Microbiol, 98,
832-838.
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T.Nonaka,
A.Kita,
J.Miura-Ohnuma,
E.Katoh,
N.Inagaki,
T.Yamazaki,
and
K.Miki
(2005).
Crystal structure of putative N-acetyl-gamma-glutamyl-phosphate reductase (AK071544) from rice (Oryza sativa).
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Proteins, 61,
1137-1140.
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PDB code:
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C.R.Faehnle,
J.Blanco,
and
R.E.Viola
(2004).
Structural basis for discrimination between oxyanion substrates or inhibitors in aspartate-beta-semialdehyde dehydrogenase.
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Acta Crystallogr D Biol Crystallogr, 60,
2320-2324.
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PDB codes:
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J.Blanco,
R.A.Moore,
C.R.Faehnle,
D.M.Coe,
and
R.E.Viola
(2004).
The role of substrate-binding groups in the mechanism of aspartate-beta-semialdehyde dehydrogenase.
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Acta Crystallogr D Biol Crystallogr, 60,
1388-1395.
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PDB codes:
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J.Blanco,
R.A.Moore,
C.R.Faehnle,
and
R.E.Viola
(2004).
Critical catalytic functional groups in the mechanism of aspartate-beta-semialdehyde dehydrogenase.
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Acta Crystallogr D Biol Crystallogr, 60,
1808-1815.
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B.A.Manjasetty,
J.Powlowski,
and
A.Vrielink
(2003).
Crystal structure of a bifunctional aldolase-dehydrogenase: sequestering a reactive and volatile intermediate.
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Proc Natl Acad Sci U S A, 100,
6992-6997.
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PDB code:
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J.Blanco,
R.A.Moore,
and
R.E.Viola
(2003).
Capture of an intermediate in the catalytic cycle of L-aspartate-beta-semialdehyde dehydrogenase.
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Proc Natl Acad Sci U S A, 100,
12613-12617.
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PDB codes:
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J.Blanco,
R.A.Moore,
V.Kabaleeswaran,
and
R.E.Viola
(2003).
A structural basis for the mechanism of aspartate-beta-semialdehyde dehydrogenase from Vibrio cholerae.
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Protein Sci, 12,
27-33.
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PDB codes:
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M.Goto,
Y.Agari,
R.Omi,
I.Miyahara,
and
K.Hirotsu
(2003).
Expression, purification and preliminary X-ray characterization of N-acetyl-gamma-glutamyl-phosphate reductase from Thermus thermophilus HB8.
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Acta Crystallogr D Biol Crystallogr, 59,
356-358.
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E.Johansson,
J.J.Steffens,
Y.Lindqvist,
and
G.Schneider
(2000).
Crystal structure of saccharopine reductase from Magnaporthe grisea, an enzyme of the alpha-aminoadipate pathway of lysine biosynthesis.
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Structure, 8,
1037-1047.
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PDB codes:
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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
