Disease relevance of PRSS7

• One group (3 patients) was diagnosed as Schwachman-Diamond syndrome with pancreatic insufficiency and normal mucosal and intraluminal enterokinase activity [1].
• Nine patients with cystic fibrosis and pancreatic insufficiency had normal mucosal enterokinase activity and elevated intraluminal enterokinase activity with very low or no trypsin activity [1].
• Patients with hypoproteinemia and gastrointestinal protein loss, associated with intestinal lymphangiectasia (4 patients) and intestinal lymphoid nodular hyperplasia (3 patients), had normal or insignificant decrease of enterokinase and trypsin activities [1].
• The putative mature protease domain preceded by H(6)DDDDK was produced in Escherichia coli, purified, and successfully activated by immobilized enterokinase [2].
• After correction for enterokinase activatable activity, and specifically in the absence of calcium, the R122C mutant was more resistant to autolysis than the wild type and autoactivated more rapidly at pH 8 [3].

High impact information on PRSS7

• Nanomolar enterokinase concentrations are required to activate this new receptor, in contrast to the picomolar thrombin concentrations that activate wild-type thrombin receptor [4].
• The heavy chain achors enterokinase in the intestinal brush border membrane and the light chain is the catalytic subunit, which has the same mechanism of action as trypsin and chymotrypsin [5].
• The serine protease enterokinase is the physiological activator of trypsinogen and has a specificity for the sequence (Asp)4-Lys-Ile [5].
• Many properties of enterokinase resemble blood-clotting enzymes, suggesting that enterokinase lies on the same phylogenetic branch as the blood-clotting proteins [5].
• A normal sweat chloride with small intestinal histology, and nondetectable trypsin activity in the duodenal fluid should alert the physician to the possibility of isolated enterokinase deficiency [6].

Chemical compound and disease context of PRSS7

• Pancreatitis was induced by intraductal injection of sodium-taurocholate (3%, 1 mL/kg BW) and enterokinase (2 U/kg BW) [7].
• Isolation of high-enterokinase-secreting segments of small bowel from their luminal continuity by fashioning of Thiry--Vella fistulas led to a decay of enterokinase activity to minimal levels within 12--16 h [8].
• Procedures have been devised for producing in Escherichia coli high yields of purified recombinant human growth hormone (hGH), by utilizing N-terminal pentapeptide sequence of human tumor necrosis factor-alpha, histidine tag and enterokinase cleavage site as a fusion partner [9].

Biological context of PRSS7

• However, our results showed that only two genes (COL6A1 and PRSS7), among 24 genes on chromosome 21, were down-regulated in the AF cells of DS [10].
• The deduced amino acid sequences indicate that active two-chain enterokinase is derived from a single-chain precursor [11].
• The enterokinase gene was localized to human chromosome 21q21 by fluorescence in situ hybridization [12].
• Between 26 to 30 weeks of gestation, the EK activity is only 6% and full term babies (40 weeks) 20% of that found in older children [13].
• The utility of CLiPS was demonstrated by determining the substrate specificity of two unrelated proteases, caspase-3 and enteropeptidase (or enterokinase) [14].

Anatomical context of PRSS7

• Enteropeptidase (enterokinase [E.C.3.4.21.9]) is a serine protease of the intestinal brush border in the proximal small intestine [15].
• Enterokinase is a serine protease of the duodenal brush border membrane that cleaves trypsinogen and produces active trypsin, thereby leading to the activation of many pancreatic digestive enzymes [12].
• Fourteen patients with diarrhea and grade II mucosal injury revealed a significant (P less than 0.01) reduction of enterokinase, trypsin, and disaccharidase activites as compared to 59 children with normal mucosa [1].
• In addition, the distributional pattern of EK differs from the disaccharidases, showing the highest activity in duodenum and the lowest in ileum, whereas disaccharidases are highest in jejunum with lower activity in duodenum and ileum [13].
• The concomitant appearance of enterokinase (EK) and trypsin activities in the human intestinal mucosa is indicative of the importance of EK as an activator of trypsinogen and therefore as the key enzyme in protein digestion [13].

Associations of PRSS7 with chemical compounds

• After isopropyl beta-D-thiogalactoside induction, the M(r) 37,000 His(10)-tagged Ang-CD30L was directed into the periplasmic space and functionally purified by a combination of metal ion affinity followed by enterokinase cleavage of the His(10)-Tag and molecular size chromatography [16].
• Transfection of enterokinase-unresponsive cells with this construct conferred both enterokinase-sensitive phosphoinositide hydrolysis and inhibition of adenylyl cyclase [17].
• After removal of the purification tag/enterokinase site by enterokinase digestion, rMCP-5 bound the serine-protease-specific inhibitor diisopropyl fluorophosphate, showing that rMCP-5 was catalytically active [18].
• These findings would suggest that the ability of hepatocytes to degrade enterokinase cleared from the blood may be bypassed or impaired by prolonged ethanol consumption and a deficient diet [19].
• In the absence of heparin, barely detectable enzyme activity was obtained after enterokinase cleavage of 6xHis-EK-mMCP-6 over a pH range of 5.5-7 [20].

Regulatory relationships of PRSS7

• The amino acid sequence surrounding the amino terminus of the enterokinase light chain is ITPK-IVGG (human) or VSPK-IVGG (bovine), suggesting that single-chain enterokinase is activated by an unidentified trypsin-like protease that cleaves the indicated Lys-Ile bond [11].
• The purified mutant hK2 may be activated by either enterokinase or factor Xa to generate an enzyme for use in functional studies with the characteristics of the original wild-type protein [21].
• In the present study, we produced a secreted form of recombinant MT-SP1/matriptase (ekMT-SP1s) that can be activated by enterokinase in vitro and investigated the inhibitory ability of various protease inhibitors toward the recombinant enzyme [22].

Other interactions of PRSS7

• When [125I]-PSTI was incubated with pure trypsin, chymotrypsin, elastase or enterokinase greater than 95% of tracer eluted in the position of PSTI-enzyme complex [23].
• Unfortunately, the conditions necessary for the removal of the peptide by enterokinase resulted in incomplete protease digestion and substantial loss of NAT1 activity [24].
• In contrast to these growth-promoting effects, administration of ghrelin reduced expression of mRNA for pepsin in the stomach and was without effect on expression of mRNA for enterokinase in the duodenum [25].
• Full-length human genes for HDAC1 and HDAC3 were cloned into the pcDNA 3.1 vector containing a N-terminal His-tag with an enterokinase cleavage site [26].
• We expressed human granzyme A in bacteria as a proenzyme capable of in vitro activation by enterokinase [27].

Analytical, diagnostic and therapeutic context of PRSS7

• By Northern blotting, a 4.4 kb enterokinase mRNA was detected only in small intestine [12].
• The distribution of enterokinase in human intestine was studied in operative mucosal biopsies using specific antiserum to human enterokinase, previously purified to apparent homogeneity by affinity chromatography and immunoabsorption [28].
• The proportion of enterokinase appearing in catalytically active form in bile after intravenous injection was substantially greater in the ethanol-maintained animals than the isocaloric controls; the difference was highly significant (p less than 0.001) and reached two- to four-fold after 70 days on the diet [19].
• The apparent molecular weights of human intestinal aminopeptidase, enterokinase and maltase in native duodenal fluid were estimated by gel chromatography on Sephadex G-200 under different conditions of operational buffer and temperature [29].
• If the enterokinase was allowed to decay over 24 h its activity could be restored to 80 per cent of its normal level by perfusion for 24 h with trypsin and sodium [8].

References