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PDBsum entry 1y0y
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Hydrolase/hydrolase inhibitor
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PDB id
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1y0y
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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 tet protease reveals complementary protein degradation pathways in prokaryotes.
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Authors
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L.Borissenko,
M.Groll.
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Ref.
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J Mol Biol, 2005,
346,
1207-1219.
[DOI no: ]
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PubMed id
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Abstract
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Protein degradation is an essential and strictly controlled process with
proteasome and functionally related proteases representing its central part.
Tricorn protease (TRI) has been shown to act downstream of the proteasome,
degrading produced peptides. Recently, a novel large prokaryotic aminopeptidase
oligomeric complex, named TET, has been identified. This complex degrades
peptides of different length in organisms where TRI is not present. We
determined the crystal structure of TET from the thermophilic archaeon
Pyrococcus horikoshii at 1.6 A resolution in native form and in complex with the
inhibitor amastatin. We demonstrate that, beside the novel tetrahedral
oligomerisation pattern, TET possesses a unique mechanism of substrate
attraction and orientation. TET sequentially degrades peptides produced by the
proteasome to single amino acids. Furthermore, we reconstituted in vitro the
minimal protein degradation system from initial unfolding of labelled protein
substrates, up to release of free amino acids. We propose that TET and TRI act
as functional analogues in different organisms, with TET being more widely
distributed. Thus, TET and TRI represent two evolutionarily diverged pathways of
peptide degradation in prokaryotes.
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Figure 4.
Figure 4. Surface representation of the TET complex, colour
coded according to its electrostatic potential contoured from
-15 kT/e (intense red) to 15 kT/e (intense blue). (a) Stereo
representation of the oligomeric TET complex. The molecule is
oriented along its 3-fold symmetry axis with the central opening
facing the reader. (b) Two halves of the complex in cut-open
surface representation, viewed along the 3-fold axis. The
central pore, indicated by the grey surfaces, measures about 60
Å in diameter. Inhibitor molecules (green) are bound to
the active centres, Zn2+ atoms are coloured in magenta. Left:
The three openings for exit of the produced amino acids (9
Å in diameter) are clearly seen in proximity to the
central opening (18 Å in diameter). Right: the cluster of
positively charged arginine residues (blue, in the centre)
facilitates redirection of the substrate peptides' amino termini
to the adjacent positively charged specificity pockets (red,
with bound inhibitor).
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Figure 5.
Figure 5. Proteolytic pathways in prokaryotes.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2005,
346,
1207-1219)
copyright 2005.
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