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PDBsum entry 1itq
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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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Crystal structure of human renal dipeptidase involved in beta-Lactam hydrolysis.
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Authors
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Y.Nitanai,
Y.Satow,
H.Adachi,
M.Tsujimoto.
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Ref.
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J Mol Biol, 2002,
321,
177-184.
[DOI no: ]
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PubMed id
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Abstract
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Human renal dipeptidase is a membrane-bound glycoprotein hydrolyzing dipeptides
and is involved in hydrolytic metabolism of penem and carbapenem beta-lactam
antibiotics. The crystal structures of the saccharide-trimmed enzyme are
determined as unliganded and inhibitor-liganded forms. They are informative for
designing new antibiotics that are not hydrolyzed by this enzyme. The active
site in each of the (alpha/beta)(8) barrel subunits of the homodimeric molecule
is composed of binuclear zinc ions bridged by the Glu125 side-chain located at
the bottom of the barrel, and it faces toward the microvillar membrane of a
kidney tubule. A dipeptidyl moiety of the therapeutically used cilastatin
inhibitor is fully accommodated in the active-site pocket, which is small enough
for precise recognition of dipeptide substrates. The barrel and active-site
architectures utilizing catalytic metal ions exhibit unexpected similarities to
those of the murine adenosine deaminase and the catalytic domain of the
bacterial urease.
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Figure 1.
Figure 1. The overall view of the hrDP. (a) The dimeric
structure of the hrDP viewed from the membrane-binding side.
Ser369 anchored to the membrane is located on the C-terminal
end, and the active sites are located on this side. The
a-helices and the b-strands composing (a/b)[8] barrels are shown
in green and yellow, respectively, and the a-helices capping the
barrels are shown in magenta. Zinc ions are drawn as red
spheres; cysteine residues forming disulfide bonds are drawn as
yellow ball-and-sticks; N-linked N-acetylglucosamine molecules
are drawn as pink ball-and-sticks. (b) The dimer viewed from a
90° rotation along the long axis of the dimer. (c) Stereo
representation of a monomer subunit. (d) A drawing of the
folding of the monomer subunit. The strands or helices are drawn
to reflect their relative lengths. The color scheme and labels
are consistent with those in (a) to (c). All Figures except
Figure 2(a) and (c) were produced with MOLSCRIPT [30.] and
Raster3D. [31.]
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Figure 3.
Figure 3. Comparison of the architectures of the
metallo-hydrolases having disordered (a/b)[8] barrels. (a)
Arrangement of b-strands composing the barrels. Corresponding
main-chain atoms of the b-strands are superimposed by
least-squares fitting. The strands of subunit A of the hrDP are
shown as yellow arrows; urease in sky-blue, phosphotriesterase
in orange, and adenosine deaminase in red. The strands labeled
b1 through b8 are sequentially arranged from the N-terminal side
in each polypeptide. (b) Superimposition of the metal ions and
ligands through least-squares fitting. The metal ions and ligand
groups of the hrDP subunit A are drawn in yellow, urease in
sky-blue, and phosphotriesterase in orange. Carbamoyllysine
ligands are represented with Carb-K labels. The fittings in (a)
and (b) were calculated independently.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2002,
321,
177-184)
copyright 2002.
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Secondary reference #1
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Title
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Crystallization and preliminary X-Ray investigation of a glycoprotein, Human renal dipeptidase
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Authors
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Y.Nitanai,
Y.Satow,
H.Adachi,
M.Tsujimoto.
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Ref.
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j cryst growth, 1996,
168,
280.
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