Get   for     ? 
 Site search     ? 
Catalytic Site Atlas Version 2.2.12
Find Annotated Site: PDB code:
Swiss-Prot code:
EC number:
Help
CSA entry for 1k32
Original Entry
Title:
Hydrolase
Compound:
Tricorn protease
Mutant:
No
UniProt/Swiss-Prot:
P96086-TRI_THEAC
EC Class:
3.4.21.-
Other CSA Entries:
Overview of all sites for 1k32
Homologues of 1k32
Entries for UniProt/Swiss-Prot: P96086
Entries for EC: 3.4.21.-
Other Databases:
PDB entry: 1k32
PDBsum entry: 1k32
UniProt/Swiss-Prot: P96086
IntEnz entry: 3.4.21.-
Literature Report:
Introduction:
The tricorn protease is the core of a proteolytic system identified in the model organism Thermoplasma acidophilum. This complex functions to degrade the 7-9 residue peptides that are produced by the proteasome-mediated degradation of cellular proteins. The basic functional unit of the tricorn protease is a homohexamer of the 121 kDa subunit; however electron microscopy studies indicate that 20 copies of this 720 kDa hexamer can assemble further in vivo to form a giant 14.6 MDa icosahedral capsid.
Mechanism:
The tricorn protease is thought to use a mechanism similar to that of the trypsin-like serine proteases. His 746 deprotonates Ser 965 which attacks the peptide bond to form a tetrahedral intermediate. Accumulation of negative charge on the carbonyl oxygen during formation of the tetrahedral intermediate is stabilised by an oxyanion hole composed of the backbone NH groups of Gly 918 and Asp 966. Collapse of the tetrahedral intermediate with protonation of the departing leaving group by His 746 generates and acyl-enzyme intermediate; this is subsequently hydrolysed by a water molecule that is deprotonated by His 746.
Sites:

Click to Display Catalytic Site (Get help with this section)
Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
HISA 746 746Sidechain
Acid/baseSubstrate
Acid/baseResidue
Acid/baseWater
Deprotonates Ser 965. Protonates the departing amine nitrogen during collapse of the tetrahedral intermediate. Deprotonates the water molecule that hydrolyses the acyl-enzyme intermediate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11719810 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 11719810 Current protein Mutagenesis of residue

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLYA 918 918Backbone amide
ElectrostaticTransition state
Backbone NH forms part of the oxyanion hole that stabilises the tetrahedral intermediate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11719810 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
SERA 965 965Sidechain
NucleophileSubstrate
Acts as a nucleophile to attack the peptide bond and form an acyl-enzyme intermediate which is subsequently hydrolysed.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11719810 Current protein Residue is covalently bound to intermediate, based on structural data
PubMed ID 11719810 Current protein Mutagenesis of residue

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ASPA 966 966Backbone amide
ElectrostaticTransition state
Backbone NH forms part of the oxyanion hole that stabilises the tetrahedral intermediate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11719810 Current protein Residue is positioned appropriately (ligand position known)
Notes:
His 746 is correctly orientated by the O-gamma of Ser 745, which in turn is polarised by Glu 1023.
References:
1
Crystal structure of the tricorn protease reveals a protein disassembly line.
H. Brandstetter and J. S. Kim and M. Groll and R. Huber
Nature 414, (6862) 466-70, (2001).
11719810
Which EBI biological databases are available and how do I access them? EBI Site Map