PDBsum entry 3v6e

Hydrolase/signaling protein

PDB id: 3v6e

Contents

Protein chains

328 a.a.

81 a.a.

Ligands

GOL

Metals

_ZN

_CL ×2

Waters ×198

PDB id:

3v6e

Name:

Hydrolase/signaling protein

Title:

Crystal structure of usp2 and a mutant form of ubiquitin

Structure:

Ubiquitin carboxyl-terminal hydrolase 2. Chain: a. Synonym: 41 kda ubiquitin-specific protease, deubiquitinating enzyme 2, ubiquitin thiolesterase 2, ubiquitin-specific-processing protease 2. Engineered: yes. Ubiquitin. Chain: b. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ubp41, usp02.258.605, usp2. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: ubc.

Resolution:

2.10Å R-factor: 0.177 R-free: 0.234

Authors:

M.Neculai,A.Ernst,S.Sidhu,C.H.Arrowsmith,A.M.Edwards,C.Bountra, J.Weigelt,S.Dhe-Paganon,Structural Genomics Consortium (Sgc)

Key ref:

A.Ernst et al. (2013). A strategy for modulation of enzymes in the ubiquitin system. Science, 339, 590-595. PubMed id: 23287719

Date:

19-Dec-11 Release date: 19-Dec-12

Protein chain

O75604  (UBP2_HUMAN) -  Ubiquitin carboxyl-terminal hydrolase 2 from Homo sapiens

Seq: 605 a.a.

Struc: 328 a.a.

Protein chain

P0CG48  (UBC_HUMAN) -  Polyubiquitin-C from Homo sapiens

Seq: 685 a.a.

Struc: 81 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chain A: E.C.3.4.19.12 - ubiquitinyl hydrolase 1.
• Reaction: Thiol-dependent hydrolysis of ester, thiolester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
• Enzyme class 3: Chain B: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Science 339:590-595 (2013)

PubMed id: 23287719

A strategy for modulation of enzymes in the ubiquitin system.

A.Ernst, G.Avvakumov, J.Tong, Y.Fan, Y.Zhao, P.Alberts, A.Persaud, J.R.Walker, A.M.Neculai, D.Neculai, A.Vorobyov, P.Garg, L.Beatty, P.K.Chan, Y.C.Juang, M.C.Landry, C.Yeh, E.Zeqiraj, K.Karamboulas, A.Allali-Hassani, M.Vedadi, M.Tyers, J.Moffat, F.Sicheri, L.Pelletier, D.Durocher, B.Raught, D.Rotin, J.Yang, M.F.Moran, S.Dhe-Paganon, S.S.Sidhu.

ABSTRACT

The ubiquitin system regulates virtually all aspects of cellular function. We report a method to target the myriad enzymes that govern ubiquitination of protein substrates. We used massively diverse combinatorial libraries of ubiquitin variants to develop inhibitors of four deubiquitinases (DUBs) and analyzed the DUB-inhibitor complexes with crystallography. We extended the selection strategy to the ubiquitin conjugating (E2) and ubiquitin ligase (E3) enzymes and found that ubiquitin variants can also enhance enzyme activity. Last, we showed that ubiquitin variants can bind selectively to ubiquitin-binding domains. Ubiquitin variants exhibit selective function in cells and thus enable orthogonal modulation of specific enzymatic steps in the ubiquitin system.