The serine protease inhibitor C1-Inhibitor (C1-Inh) inhibits several complement- and contact-system proteases, which play an important role in inflammation. C1-Inh has a short reactive site loop (RSL) compared to other serpins. RSL length determines the inhibitory activity of serpins. We investigated the effect of RSL elongation on inhibitory activity of C1-Inh by insertion of one or two alanine residues in the RSL. One of five mutants had an increased association rate with kallikrein, but was nevertheless a poor inhibitor because of a simultaneous high stoichiometry of inhibition (>10). The association rate of the other variants was lower than that of wild-type C1-Inh. These data suggest that the relatively weak inhibitory activity of C1-Inh is not the result of its short RSL. The short RSL of C1-Inh has, surprisingly, the optimal length for inhibition.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbapap.2004.02.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Exposure to Rifampicin and its Metabolite 25-Deacetylrifampicin Rapidly Decreases During Tuberculosis Therapy.
Clin Pharmacokinet
January 2025
Facultés de Médecine et de Pharmacie de Lyon, Univ Lyon, Université Claude Bernard Lyon 1, Lyon, France.
Background And Objective: Limited information is available on the pharmacokinetics of rifampicin (RIF) along with that of its active metabolite, 25-deacetylrifampicin (25-dRIF). This study aimed to analyse the pharmacokinetic data of RIF and 25-dRIF collected in adult patients treated for tuberculosis.
Methods: In adult patients receiving 10 mg/kg of RIF as part of a standard regimen for drug-susceptible pulmonary tuberculosis enrolled in the Opti-4TB study, plasma RIF and 25-dRIF concentrations were measured at various occasions.
Targeting p38γ synergistically enhances sorafenib-induced cytotoxicity in hepatocellular carcinoma.
Cell Biol Toxicol
January 2025
Division of Abdominal Tumor Multimodality Treatment, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan Province, China.
Sorafenib (Sora) is a first-line treatment for patients with advanced hepatocellular carcinoma (HCC). It can significantly improve the survival rate of patients with advanced HCC, but it is prone to drug resistance during treatment, so the therapeutic effect is extremely limited. Here, we demonstrate that an elevated expression of protein kinase p38γ in hepatocellular carcinoma cells diminishes the tumor cells' sensitivity to Sora.
View Article and Find Full Text PDFAcute Concurrent Exercise Improves Inhibitory Control Without Mediating the Role of Lactate: An Event-Related Potential Study.
Sports Med Open
January 2025
Department of Physical Education and Sport Sciences, National Taiwan Normal University, 162, Section 1, Heping E. Road, Taipei, 106, Taiwan.
Background: Concurrent exercise (CE), an emerging exercise modality characterized by sequential bouts of aerobic (AE) and resistance exercise (RE), has demonstrated acute benefits on executive functions (EFs) and neuroelectric P3 amplitude. However, the effect of acute CE on inhibitory control, a sub-component of EFs, and P3 amplitude remains inconclusive. Moreover, exploring the mechanisms underlying the effects of acute exercise on EFs contributes to scientific comprehension, with lactate recognized as a crucial candidate positively correlated with EFs.
View Article and Find Full Text PDFc-di-GMP inhibits rRNA methylation and impairs ribosome assembly in the presence of kanamycin.
EMBO Rep
January 2025
Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.
Cyclic diguanosine monophosphate (c-di-GMP) is a ubiquitous bacterial secondary messenger with diverse functions. A previous Escherichia coli proteome microarray identified that c-di-GMP binds to the 23S rRNA methyltransferases RlmI and RlmE. Here we show that c-di-GMP inhibits RlmI activity in rRNA methylation assays, and that it modulates ribosome assembly in the presence of kanamycin.
View Article and Find Full Text PDFThe ejaculatory reflex consists of emission and expulsion, with the latter involving rhythmic muscular contractions that propel seminal fluid. Botulinum toxin, through its inhibitory effects, has been hypothesized to improve premature ejaculation (PE). This study evaluates high-quality evidence on botulinum toxin-A injections into the bulbospongiosal muscle as a treatment for PE.
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!