Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017160 (gastroenteritis)
 11,398 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Bolesatine is a toxic protein (LD50 oral 3.3 mg/kg in mice) isolated from the mushroom Boletus satanas Lenz, which inhibits protein synthesis in vitro. It induces gastroenteritis in human. 2. 14C-Bolesatine, given orally to rats (30 micrograms/kg), is distributed in the gastrointestinal, tract, kidney, liver and, to a lesser extent, in the thymus, spleen and lung. Bolesatine is eliminated in faeces and urine (80% in 24h). 3. The material excreted in urine is not proteolysed, and no protease (trypsin, chymotrypsin, pronase, proteinase K, Staphylococcus aureus (strain V8) protease and pepsin) is found to hydrolyse bolesatine in either its native or denatured form. However, thermolysin hydrolysed denatured bolesatine to a protein having a Mr of about 55 kD. 4. Bolesatine is found in all the following rat liver and kidney subcellular fractions: cytoplasm, mitochondria, ribosomes, microsomes and nuclei.
 ...
PMID:Disposition of the toxic protein, bolesatine, in rats: its resistance to proteolytic enzymes. 200 68

Human noroviruses are highly infectious viruses that cause the majority of acute, non-bacterial epidemic gastroenteritis cases worldwide. The first open reading frame of the norovirus RNA genome encodes for a polyprotein that is cleaved by the viral protease into six non-structural proteins. The first non-structural protein, NS1-2, lacks any significant sequence similarity to other viral or cellular proteins and limited information is available about the function and biophysical characteristics of this protein. Bioinformatic analyses identified an inherently disordered region (residues 1-142) in the highly divergent N-terminal region of the norovirus NS1-2 protein. Expression and purification of the NS1-2 protein of Murine norovirus confirmed these predictions by identifying several features typical of an inherently disordered protein. These were a biased amino acid composition with enrichment in the disorder promoting residues serine and proline, a lack of predicted secondary structure, a hydrophilic nature, an aberrant electrophoretic migration, an increased Stokes radius similar to that predicted for a protein from the pre-molten globule family, a high sensitivity to thermolysin proteolysis and a circular dichroism spectrum typical of an inherently disordered protein. The purification of the NS1-2 protein also identified the presence of an NS1-2 dimer in Escherichia coli and transfected HEK293T cells. Inherent disorder provides significant advantages including structural flexibility and the ability to bind to numerous targets allowing a single protein to have multiple functions. These advantages combined with the potential functional advantages of multimerisation suggest a multi-functional role for the NS1-2 protein.
 ...
PMID:Inherent structural disorder and dimerisation of murine norovirus NS1-2 protein. 2234 81

Vibrio cholerae of serogroup O1 and O139, the etiological agent of the diarrheal disease cholera, expresses the extracellular Zn-dependent metalloprotease hemagglutinin (HA)/protease also reported as vibriolysin. This enzyme is also produced by non-O1/O139 (non-cholera) strains that cause mild, sporadic illness (i.e. gastroenteritis, wound or ear infections). Orthologs of HA/protease are present in other members of the Vibrionaceae family pathogenic to humans and fish. HA/protease belongs to the M4 neutral peptidase family and displays significant amino acid sequence homology to Pseudomonas aeruginosa elastase (LasB) and Bacillus thermoproteolyticus thermolysin. It exhibits a broad range of potentially pathogenic activities in cell culture and animal models. These activities range from the covalent modification of other toxins, the degradation of the protective mucus barrier and disruption of intestinal tight junctions. Here we review (i) the structure and regulation of HA/protease expression, (ii) its interaction with other toxins and the intestinal mucosa and (iii) discuss the possible role(s) of HA/protease in the pathogenesis of cholera.
...
PMID:Vibrio cholerae hemagglutinin(HA)/protease: An extracellular metalloprotease with multiple pathogenic activities. 2695 44