AI Article Synopsis
- USP4 is a deubiquitinating enzyme involved in spliceosome regulation, and its structure includes a typical USP-like fold with a ubiquitin-binding site.
- A ubiquitin-like (Ubl) domain within USP4 can bind to the catalytic region, inhibiting its activity by competing with the ubiquitin substrate.
- Other USPs, like USP39, can counteract this inhibition, suggesting a regulatory interplay between different USPs.
Article Abstract
USP4 is a member of the ubiquitin-specific protease (USP) family of deubiquitinating enzymes that has a role in spliceosome regulation. Here, we show that the crystal structure of the minimal catalytic domain of USP4 has the conserved USP-like fold with its typical ubiquitin-binding site. A ubiquitin-like (Ubl) domain inserted into the catalytic domain has autoregulatory function. This Ubl domain can bind to the catalytic domain and compete with the ubiquitin substrate, partially inhibiting USP4 activity against different substrates. Interestingly, other USPs, such as USP39, could relieve this inhibition.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077250 | PMC |
| http://dx.doi.org/10.1038/embor.2011.33 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
Icahn School of Medicine at Mount Sinai Medical Center, New York, NY, USA.
Background: Presenilin1 (PS1)/γ-secretase cleaves within the transmembrane domain of numerous receptor substrates. Mutations in PS1 have implications on the catalytic subunit of γ-secretase decreasing its activity and becoming a potential causative factor for Familial Alzheimer's Disease (FAD). This work studies the role of PS1/γ-secretase on the processing, angiogenic signaling, and functions of VEGFR2 and the effects of PS1 FAD mutants on the γ-secretase-mediated epsilon cleavage of VEGFR2.
View Article and Find Full Text PDFTargeted Adherence and Enhanced Degradation of Feather Keratins by a Novel Prepeptidase C-Terminal Domain-Fused Keratinase.
J Agric Food Chem
January 2025
College of Light Industry and Food Engineering, Guangxi University, Nanning 530004, People's Republic of China.
Keratinases are valuable enzymes for converting feather keratin waste into bioactive products but often suffer from poor substrate specificity and low catalytic efficiency. This study reported the creating of a novel keratinase with targeted adherence and specific degradation on feather keratins by fusing prepeptidase C-Terminal (PPC) domain. A PPC domain of metalloprotease E423 specifically adsorbed feather keratins by hydrogen bonds and hydrophobic interactions in a time- and temperature-dependent manner.
View Article and Find Full Text PDFStructural and kinetic characterization of DUSP5 with a Di-phosphorylated tripeptide substrate from the ERK activation loop.
Front Chem Biol
August 2024
Center for Structure-based Drug Design and Development, Department of Pharmaceutical Sciences, Concordia University Wisconsin, Mequon, WI, United States.
Introduction: Dual specific phosphatases (DUSPs) are mitogen-activated protein kinase (MAPK) regulators, which also serve as drug targets for treating various vascular diseases. Previously, we have presented mechanistic characterizations of DUSP5 and its interaction with pERK, proposing a dual active site.
Methods: Herein, we characterize the interactions between the DUSP5 phosphatase domain and the pT-E-pY activation loop of ERK2, with specific active site assignments.
Biochemical properties and substrate specificity of GOB-38 in Elizabethkingia anophelis.
Sci Rep
January 2025
Department of Infectious Disease, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
The novel pathogen, Elizabethkingia anophelis, has gained attention due to its high mortality rates and drug resistance facilitated by its inherent metallo-β-lactamases (MBLs) genes. This study successfully identified and outlined the functions of the B3-Q MBLs variant, GOB-38, in a clinical sample of E. anophelis.
View Article and Find Full Text PDFFrameshift variation in the HMG-CoA reductase gene and unresponsiveness to cholesterol-lowering drugs in type 2 diabetes mellitus patients.
Sci Rep
January 2025
Department of Medical Analysis, Faculty of Applied Science, Tishk International University, KRG, Erbil, Iraq.
Dyslipidemia, an imbalance in blood lipid levels, is a frequent complication of type 2 diabetes mellitus (DM2) and heightens the risk of cardiovascular diseases (CVDs). Statins, which inhibit 3-hydroxy-3-methylglutaryl-CoA reductase, are potent competitive inhibitors that reduce plasma cholesterol levels. However, individual responses to statins can vary markedly, possibly due to genetic variations in the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!