AI Article Synopsis
- BIEP is an extracellular serine protease from Bacillus intermedius that specifically cleaves peptide bonds next to glutamic acid.
- Its unique three-dimensional structure, analyzed in two crystal forms, features a beta-sandwich domain that differs from typical chymotrypsin structures.
- The binding of a 2-methyl-2,4-pentanediol molecule in the substrate site mimics glutamic acid and reveals key residues for substrate recognition, while also disrupting interactions between crucial catalytic residues.
Article Abstract
Extracellular glutamyl endopeptidase from Bacillus intermedius (BIEP) is a chymotrypsin-like serine protease which cleaves the peptide bond on the carboxyl side of glutamic acid. Its three-dimensional structure was determined for C222(1) and C2 crystal forms of BIEP to 1.5 and 1.75 A resolution, respectively. The topology of BIEP diverges from the most common chymotrypsin architecture, because one of the domains consists of a beta-sandwich consisting of two antiparallel beta-sheets and two helices. In the C2 crystals, a 2-methyl-2,4-pentanediol (MPD) molecule was found in the substrate binding site, mimicking a glutamic acid. This enabled the identification of the residues involved in the substrate recognition. The presence of the MPD molecule causes a change in the active site; the interaction between two catalytic residues (His47 and Ser171) is disrupted. The N-terminal end of the enzyme is involved in the formation of the substrate binding pocket. This indicates a direct relation between zymogen activation and substrate charge compensation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/bi035354s | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Necrotic activity of ExhC from Mammaliicoccus sciuri is mediated by specific amino acid residues.
Int J Biol Macromol
January 2024
Multiuser Center for Biomolecular Innovation, São Paulo State University - UNESP, São José do Rio Preto, SP, Brazil. Electronic address:
Mammaliicoccus sciuri, a commensal and pathogenic bacterium of significant clinical and veterinary relevance, expresses exfoliative toxin C (ExhC), a specific glutamyl endopeptidase belonging to the chymotrypsin family as the principal virulence factor. However, unlike most members of this family, ETs are inactive against a wide range of substrates and possess exquisite specificity for desmoglein-1 (Dsg1), a cadherin-like adhesion molecule that is crucial to maintain tissue integrity, thereby preventing the separation of skin cells and the entry of pathogens. ExhC is of clinical importance since in addition to causing exfoliation in pigs and mice, it induces necrosis in multiple mammalian cell lines, a property not observed for other ETs.
View Article and Find Full Text PDFPotential elevation of exopeptidase activity of Glu-specific endopeptidase I/GluV8 mediated by hydrophobic P1'-position amino acid residue.
Biochimie
May 2024
Department of Pediatric Dentistry, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8588, Japan; Division of Molecular Microbiology, Department of Microbiology, Iwate Medical University, 1-1-1 Idai-dori, Yahaba-cho, Iwate, 028-3694, Japan. Electronic address:
We recently reported that the activities of dipeptidyl-peptidase (DPP)7 and DPP11, S46-family exopeptidases were significantly elevated by the presence of prime-side amino acid residues of substrates caused by an increase in k [Ohara-Nemoto Y. et al., J Biol Chem 298(3):101585.
View Article and Find Full Text PDFCeliac disease (CeD) is an immune-mediated chronic disorder triggered by the ingestion of wheat gluten in genetically predisposed individuals. Gluten is a major food ingredient, infamously containing proline and glutamine-rich domains that are highly resistant to digestion by mammalian proteolytic enzymes. Thus, adhering to a gluten-free diet (GFD) is the only known treatment for CeD, albeit with many complications.
View Article and Find Full Text PDFConstruction of an attenuated glutamyl endopeptidase deletion strain of Nocardia seriolae.
Fish Shellfish Immunol
October 2022
Fisheries College of Guangdong Ocean University, Guangdong Provincial Key Laboratory of Pathogenic Biology and Epidemiology for Aquatic Economic Animals, Zhanjiang, 524088, China; Shenzhen Institute of Guangdong Ocean University, Guangdong Provincial Engineering Research Center for Aquatic Animal Health Assessment, Shenzhen Public Service Platform for Evaluation of Marine Economic Animal Seedings, Shenzhen, 518120, China. Electronic address:
The glutamyl endopeptidase homolog of Nocardia seriolae (GluNS) has been proved to be a potential virulence factor in our previous study. Present investigation was carried out to construct an attenuated N. seriolae strain by deletion with GluNS gene and evaluate its protective immunity in head snakehead.
View Article and Find Full Text PDFTargeting of gallbladder megalin receptors with DHA-conjugated limonene albumin nanoparticles.
Nanoscale
April 2022
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Gallbladder stones are a major pathogenic factor leading to cholecystitis, and it is increasingly important to explore innovative drug delivery methods for gallstones. In the present study, docosahexaenoic acid-coupled limonene bovine serum albumin nanoparticles (LIM-DHA-BSA-NPs) were constructed. The LIM-DHA-BSA-NPs are spherical structures, and the distribution was relatively uniform, and, more importantly, it has low cytotoxicity and good safety.
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!