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PDBsum entry 1poj
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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X-Ray structure of isoaspartyl dipeptidase from e.Coli: a dinuclear zinc peptidase evolved from amidohydrolases.
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Authors
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D.Jozic,
J.T.Kaiser,
R.Huber,
W.Bode,
K.Maskos.
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Ref.
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J Mol Biol, 2003,
332,
243-256.
[DOI no: ]
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PubMed id
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Abstract
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L-aspartyl and L-asparaginyl residues in proteins spontaneously undergo
intra-residue rearrangements forming isoaspartyl/beta-aspartyl residues linked
through their side-chain beta-carboxyl group with the following amino acid. In
order to avoid accumulation of isoaspartyl dipeptides left over from protein
degradation, some bacteria have developed specialized isoaspartyl/beta-aspartyl
zinc dipeptidases sequentially unrelated to other peptidases, which also poorly
degrade alpha-aspartyl dipeptides. We have expressed and crystallized the 390
amino acid residue isoaspartyl dipeptidase (IadA) from E.coli, and have
determined its crystal structure in the absence and presence of the phosphinic
inhibitor Asp-Psi[PO(2)CH(2)]-LeuOH. This structure reveals an octameric
particle of 422 symmetry, with each polypeptide chain organized in a
(alphabeta)(8) TIM-like barrel catalytic domain attached to a U-shaped
beta-sandwich domain. At the C termini of the beta-strands of the beta-barrel,
the two catalytic zinc ions are surrounded by four His, a bridging carbamylated
Lys and an Asp residue, which seems to act as a proton shuttle. A large
beta-hairpin loop protruding from the (alphabeta)(8) barrel is disordered in the
free peptidase, but forms a flap that stoppers the barrel entrance to the active
center upon binding of the dipeptide mimic. This isoaspartyl dipeptidase shows
strong topological homology with the alpha-subunit of the binickel-containing
ureases, the dinuclear zinc dihydroorotases, hydantoinases and
phosphotriesterases, and the mononuclear adenosine and cytosine deaminases,
which all are catalyzing hydrolytic reactions at carbon or phosphorous centers.
Thus, nature has adapted an existing fold with catalytic tools suitable for
hydrolysis of amide bonds to the binding requirements of a peptidase.
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Figure 1.
Figure 1. Stereo view of the quarternary assembly of
isoaspartyl dipeptidase (IadA). (a) The octamer can be regarded
as a tetramer of dimers with the indicated 422 symmetry. The
nomenclature of the monomers as well as the location of the
active site zincs (magenta spheres) are given. The monomers in
the foreground are colored in light green (A), orange (B), green
(C), and blue (D), the monomers in the background are colored in
gray. Dimers are formed between molecules A-E, B-F, C-G and D-H,
respectively. (b) Surface of isoaspartyl dipeptidase. The
electrostatic potential was calculated with GRASP,[48.] using
charges according to Weiner and co-workers. [50.]
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Figure 5.
Figure 5. Stereo view of the structural comparison of IadA
with urease and dihydroorotase. (a) Superposition of the C^a
backbones of IadA (beige), urease (blue, PDB code 2UBP) and
dihydroorotase (green, PDB code 1J79). The structural alignment
was performed using the program TOP.[46.] (b) Superposition of
the zinc binding residues. The zinc ions of IdaA (beige) are
shown with the corresponding residues of urease (blue, PDB code
2UBP) and dihydroorotase (green, PDB code 1J79). The numbers are
according to the numbering of IadA.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2003,
332,
243-256)
copyright 2003.
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