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EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1uch

E.C. nameubiquitinyl hydrolase 1
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz)
CSA Homologues of 1uch1cmx,1xd3,2etl,2wdt,2we6,3ihr,
CSA Entries With UniProtID P15374
CSA Entries With EC Number
PDBe Entry 1uch
PDBSum Entry 1uch
MACiE Entry 1uch

Literature Report

IntroductionUbiquitin C-termainal hydrolases catalyse removal of adducts from the C-terminal of ubiquitin. Ubiquitin is added enzymatically to the side-chains of lysine residues of acceptor proteins, with polyubiquination possible. Ubiquitin C-terminal hydrolases act to free ubiquitin again from these adducts, possibly after degradation of the attached protein allowing ubiquitin cycling.
They are quite specific, cleaving only after the C-terminal glycine of ubiquitin.
MechansimThe enzyme hydrolyses the peptide bond at the C-terminus of ubiquitin to regenerate active ubiquitin from adducts with small nucleophiles. Hydrolysis occurs by attack of a Cys nucleophile using a His residue for general base catalysis. An Asp residue stabilises the protonated form of the His residue. An oxyanion hole is generated by use of a Gln residue.
In general, a very similar mechanism to the Ser/His/Asp triad of papain-like cysteine proteinases.

Catalytic Sites for 1uch

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
CysA9595macie:sideChainActs as an active site nucleophile to attack phosphodiester linkage in cleavage.
HisA169169macie:sideChainPromotes loss of the leaving group by proton donation and activates water to act as a nucleophile.
AspA184184macie:sideChainStabilises the protonated His 169.
GlnA8989macie:mainChainAmideForms an oxyanion hole for stabilisation of the transition state formed in the cleavage reaction.

Literature References

Notes:Some site mutagenesis data obtained from ubiquitin C-terminal hydrolase L1 (human).
Johnston SC
Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution.
EMBO J 1997 16 3787-3796
PubMed: 9233788
Larsen CN
Substrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues.
Biochemistry 1996 35 6735-6744
PubMed: 8639624