PDBsum entry 1y0y

Hydrolase/hydrolase inhibitor

PDB id: 1y0y

Contents

Protein chain

335 a.a. *

Ligands

L2O-VAL-VAL-ASP

Metals

_ZN ×2

Waters ×210

* Residue conservation analysis

PDB id:

1y0y

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of tetrahedral aminopeptidase from p. Horikoshii in complex with amastatin

Structure:

Frv operon protein frvx. Chain: a. Engineered: yes. Amastatin. Chain: b. Engineered: yes

Source:

Pyrococcus horikoshii. Organism_taxid: 53953. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Streptomyces sp. Me98-m3

Biol. unit:

Dodecamer (from PDB file)

Resolution:

1.60Å R-factor: 0.206 R-free: 0.222

Authors:

M.Groll,L.Borissenko

Key ref:

L.Borissenko and M.Groll (2005). Crystal structure of TET protease reveals complementary protein degradation pathways in prokaryotes. J Mol Biol, 346, 1207-1219. PubMed id: 15713475 DOI: 10.1016/j.jmb.2004.12.056

Date:

16-Nov-04 Release date: 01-Mar-05

Protein chain

O59196  (TET_PYRHO) -  Tetrahedral aminopeptidase from Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)

Seq: 353 a.a.

Struc: 335 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.11.- - ?????

DOI no: 10.1016/j.jmb.2004.12.056

J Mol Biol 346:1207-1219 (2005)

PubMed id: 15713475

Crystal structure of TET protease reveals complementary protein degradation pathways in prokaryotes.

L.Borissenko, M.Groll.

ABSTRACT

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.

Selected figure(s)

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).

Figure 5.
Figure 5. Proteolytic pathways in prokaryotes.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 346, 1207-1219) copyright 2005.

Figures were selected by an automated process.