Fidelity during cofactor assembly is essential for the proper functioning of metalloenzymes and is ensured by specific chaperones. MeaB, a G-protein chaperone for the coenzyme B12-dependent radical enzyme methylmalonyl-CoA mutase (MCM), uses the energy of GTP binding, hydrolysis or both to regulate cofactor loading into MCM, protect MCM from inactivation and rescue MCM that is inactivated during turnover. Typically, G proteins signal to client proteins using the conformationally mobile switch I and II loops. Crystallographic snapshots of MeaB reported herein reveal a new switch III element that has substantial conformational plasticity. Using alanine-scanning mutagenesis, we demonstrate that the switch III motif is critical for bidirectional signal transmission of the GTPase-activating protein activity of MCM and the chaperone functions of MeaB in the MeaB-MCM complex. Mutations in the switch III loop identified in patients corrupt this interprotein communication and lead to methylmalonic aciduria, an inborn error of metabolism.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3752380 | PMC |
| http://dx.doi.org/10.1038/nchembio.1298 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Real-world usage and effectiveness of recombinant factor IX Fc in haemophilia B from the B-SURE study in France.
Ther Adv Hematol
January 2025
Sobi, Basel, Switzerland.
Background: More real-world data are needed to complement existing phase III studies on the efficacy and safety of recombinant factor IX Fc fusion protein (rFIXFc) in people with haemophilia B.
Objectives: We report final data from the B-SURE study, evaluating the real-world usage and effectiveness of rFIXFc in France.
Methods: Previously treated patients (all ages/severities) received on-demand or prophylactic rFIXFc during B-SURE.
Environmental impact of peat alternatives in growing media for European mushroom production.
Sci Total Environ
January 2025
INAGRO, Department Edible Mushrooms, Ieperseweg 87, 8800 Rumbeke-Beitem, Belgium.
Button mushrooms are an important protein source with a production of >48 million metric tonnes in 2021. Several life cycle assessments (LCAs) have been employed in assessing mushroom cultivation. This paper assessed potential impacts of relevant alternatives (sphagnum moss, grass fibres, spent casing and bark) to peat as casing materials for mushroom production across Europe by using LCA using a cradle to farm gate approach.
View Article and Find Full Text PDFElucidating the therapeutic potential of indazole derivative bindarit against K-ras receptor: An analysis using molecular dynamics exploration.
Biochem Biophys Rep
March 2025
School of Biosciences and Technology, Vellore Institute of Technology, Vellore, India.
Ras gene is frequently mutated in cancer. Among different subtypes of Ras gene, K-Ras mutation occurs in nearly 30 % of human cancers. K-Ras mutation, specifically K-Ras (G12D) mutation is prevalent in cancers like lung, colon and pancreatic cancer.
View Article and Find Full Text PDFDeciphering the Complexities of Adult Human Steady State and Stress-Induced Hematopoiesis: Progress and Challenges.
Int J Mol Sci
January 2025
Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens (NKUA), 11527 Athens, Greece.
Human hematopoietic stem cells (HSCs) have traditionally been viewed as self-renewing, multipotent cells with enormous potential in sustaining essential steady state blood and immune cell production throughout life. Indeed, around 86% (10-10) of new cells generated daily in a healthy young human adult are of hematopoietic origin. Therapeutically, human HSCs have contributed to over 1.
View Article and Find Full Text PDFA Longer Duration of Intravenous Antibiotic Treatment for Patients with Early Periprosthetic Joint Infections Is Not Associated with a Lower Failure Rate.
Antibiotics (Basel)
January 2025
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Background: In recent years, many studies have demonstrated the efficacy of an early switch to oral antibiotics after surgical treatment in orthopedic-related infections. However, large analyses on periprosthetic joint infections (PJIs) are lacking.
Material And Methods: We conducted a retrospective observational multicenter study in patients diagnosed with an early post-operative PJI, defined as one occurring <3 months after the index arthroplasty and treated with debridement, antibiotics, and implant retention (DAIR).
Want 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!