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The differential modulation of USP activity by internal regulatory domains, interactors and eight ubiquitin chain types
- Source :
- Cell Chemistry Biology, 18(12), 1550-1561, Chemistry and Biology
- Publication Year :
- 2011
-
Abstract
- Summary Ubiquitin-specific proteases (USPs) are papain-like isopeptidases with variable inter- and intramolecular regulatory domains. To understand the effect of these domains on USP activity, we have analyzed the enzyme kinetics of 12 USPs in the presence and absence of modulators using synthetic reagents. This revealed variations of several orders of magnitude in both the catalytic turnover ( k cat ) and ubiquitin (Ub) binding ( K M ) between USPs. Further activity modulation by intramolecular domains affects both the k cat and K M , whereas the intermolecular activators UAF1 and GMPS mainly increase the k cat . Also, we provide the first comprehensive analysis comparing Ub chain preference. USPs can hydrolyze all linkages and show modest Ub-chain preferences, although some show a lack of activity toward linear di-Ub. This comprehensive kinetic analysis highlights the variability within the USP family.
- Subjects :
- Proteases
Ubiquitin-Specific Proteases
Clinical Biochemistry
Guanosine Monophosphate
Plasma protein binding
Biochemistry
03 medical and health sciences
0302 clinical medicine
Protein structure
Ubiquitin
Catalytic Domain
Drug Discovery
Endopeptidases
Humans
Enzyme kinetics
Amino Acid Sequence
Molecular Biology
Peptide sequence
030304 developmental biology
Pharmacology
0303 health sciences
biology
Chemistry
technology, industry, and agriculture
Nuclear Proteins
General Medicine
Thionucleotides
equipment and supplies
Recombinant Proteins
Protein Structure, Tertiary
Kinetics
Intramolecular force
biology.protein
Molecular Medicine
030217 neurology & neurosurgery
hormones, hormone substitutes, and hormone antagonists
Protein Binding
Subjects
Details
- ISSN :
- 18791301
- Volume :
- 18
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Chemistrybiology
- Accession number :
- edsair.doi.dedup.....dc8a753c3135876ad04b7ce8b2674a11