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PDBsum entry 1qfm
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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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Prolyl oligopeptidase: an unusual beta-Propeller domain regulates proteolysis.
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Authors
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V.Fülöp,
Z.Böcskei,
L.Polgár.
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Ref.
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Cell, 1998,
94,
161-170.
[DOI no: ]
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PubMed id
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Abstract
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Prolyl oligopeptidase is a large cytosolic enzyme that belongs to a new class of
serine peptidases. The enzyme is involved in the maturation and degradation of
peptide hormones and neuropeptides, which relate to the induction of amnesia.
The 1.4 A resolution crystal structure is presented here. The enzyme contains a
peptidase domain with an alpha/beta hydrolase fold, and its catalytic triad
(Ser554, His680, Asp641) is covered by the central tunnel of an unusual beta
propeller. This domain makes prolyl oligopeptidase an oligopeptidase by
excluding large structured peptides from the active site. In this way, the
propeller protects larger peptides and proteins from proteolysis in the cytosol.
The structure is also obtained with a transition state inhibitor, which may
facilitate drug design to treat memory disorders.
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Figure 4.
Figure 4. Comparison of the Fold of the Noncatalytic Domain
of Prolyl Oligopeptidase with a Typical β-Propeller
Structure(A) The protein chain of the β-propeller domain of
prolyl oligopeptidase is colored as in Figure 2 and viewed
perpendicular to that, down the pseudo 7-fold axis. The β
sheets of the seven blades are joined in succession (β1/1 to
β7/4, cf. Figure 1) around the central axis. The “Velcro”
is not closed; there are only hydrophobic interactions between
the first (blue) and last (green) blades. Residues (Lys82,
Glu134, His180, Asp242, Lys389, and Lys390) narrowing the
entrance to the tunnel of the propeller are shown in a
ball-and-stick representation.(B) The structure of G-protein β
subunit (PDB entry 1tbg). The “Velcro” is closed between the
two termini of the polypeptide chain by the main chain hydrogen
bonds between the N terminus (blue) and the three antiparallel
β strands from the C terminus (green). (Drawn with MolScript
and rendered with Raster3D.)
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Figure 6.
Figure 6. Surface Representation of Prolyl
OligopeptidaseThe molecular surface is superimposed on the
polypeptide chain. The picture shows a slab of the molecule,
hence the cropping of the chain. The large cavity extends from
the central tunnel of the β propeller to the catalytic domain
and is accessible through the narrow hole at the bottom of the
propeller. The covalently bound inhibitor, Z-Pro-prolinal, is
shown in a ball-and-stick representation. The molecular surface
was calculated by the method published by [11], and the figure
was prepared using XOBJECTS (M. E. M. Noble, Oxford, unpublished
program).
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The above figures are
reprinted
by permission from Cell Press:
Cell
(1998,
94,
161-170)
copyright 1998.
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