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Peptide Backbone Cleavage and Transamidation via Thioester-to-Imide Acyl Transfer.
JACS Au
January 2025
Center for Biopharmaceuticals and Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 160, DK-2100, Copenhagen, Denmark.
Cysteine thioesters are involved in a myriad of central biological transformations due to their unique reactivity. Despite their well-studied properties, we discovered an unexpected transamidation reaction of cysteine thioesters that leads to peptide backbone cleavage. -Acylcysteine-containing peptides were found to spontaneously fragment by cleavage of the amide bond in the -1 position to the acylated cysteine residue at pH 8-10.
View Article and Find Full Text PDFMolecular Basis for Short-Chain Thioester Hydrolysis by Acyl Hydrolases in -Acyltransferase Polyketide Synthases.
JACS Au
January 2025
Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K.
Polyketide synthases (PKSs) are multidomain enzymatic assembly lines that biosynthesize a wide selection of bioactive natural products from simple building blocks. In contrast to their -acyltransferase (AT) counterparts, -AT PKSs rely on stand-alone ATs to load extender units onto acyl carrier protein (ACP) domains embedded in the core PKS machinery. -AT PKS gene clusters also encode stand-alone acyl hydrolases (AHs), which are predicted to share the overall fold of ATs but function like type II thioesterases (TEs), hydrolyzing aberrant acyl chains from ACP domains to promote biosynthetic efficiency.
View Article and Find Full Text PDFChallenges in the transition of care for rare connective tissue diseases: results from the 2023 ERN ReCONNET Transition of Care Task Force survey.
Rheumatol Adv Pract
January 2025
Rheumatology Unit, ERN ReCONNET Center, IRCCS Meyer Children's Hospital, Firenze, Italy.
Objectives: Two different European Reference Networks cover CTDs with paediatric onset, the European Reference Network on Rare and Complex Connective Tissue Diseases (ERN ReCONNET) and the European Reference Network on Rare Immunological Disorders (ERN RITA). The transition of care is a significant focus, with ReCONNET centres actively addressing this through updated programs. Despite these efforts, challenges persist.
View Article and Find Full Text PDFPress-Fit Bone-Anchored Prosthesis for Individuals with Transtibial Amputation.
JBJS Essent Surg Tech
May 2024
Radboud University Medical Center, Nijmegen, The Netherlands.
Background: This video article describes the use of bone-anchored prostheses for patients with transtibial amputations, most often resulting from trauma, infection, or dysvascular disease. Large studies have shown that about half of all patients with a socket-suspended artificial limb experience limited mobility and limited prosthesis use because of socket-related problems. These problems occur at the socket-residual limb interface as a result of a painful and unstable connection, leading to an asymmetrical gait and subsequent pelvic and back pain.
View Article and Find Full Text PDFAn extracellular vesicle based hypothesis for the genesis of the polycystic kidney diseases.
Extracell Vesicle
December 2024
The Jared Grantham Kidney Institute at the University of Kansas Medical Center, Department of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Autosomal dominant polycystic kidney (ADPKD) disease is the commonest genetic cause of kidney failure (affecting 1:800 individuals) and is due to heterozygous germline mutations in either of two genes, and . Homozygous germline mutations in are responsible for autosomal recessive polycystic kidney (ARPKD) disease a rare (1:20,000) but severe neonatal disease. The products of these three genes, (polycystin-1 (PC1 4302(3)aa)), (polycystin-2 (PC2 968aa)) and (fibrocystin (4074aa)) are all present on extracellular vesicles (EVs) termed, PKD-exosome-like vesicles (PKD-ELVs).
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