Disease relevance of PREP

• The complete primary structure of the H2B(2) variant has been deduced from sets of overlapping peptides generated by CNBr cleavage, Staphylococcus aureus V8 protease, endoproteinase Arg-C, the post-proline cleaving enzyme, chymotrypsin and cleavage in dilute acid [1].
• Colonies of Anaplasma were apparent in low numbers at 9 days post exposure (PE) and infection in monolayers reached 100% by 4-5 weeks PE [2].

Psychiatry related information on PREP

• In clinical studies, abnormal plasma PO activity has been associated with bipolar disorder (BD) and schizophrenia [3].

High impact information on PREP

• Characterization of "thyroliberin-deamidating enzyme" as a post-proline-cleaving enzyme. Partial purification and enzyme-chemical analysis of the enzyme from anterior pituitary tissue [4].
• Recent studies from this laboratory have suggested a similarity, if not identity, of thyrotropin releasing factor (TRF) deamidase and post-proline cleaving enzyme [5].
• Prolyl endopeptidase (PE) belongs to a group of enzymes that specifically recognise the imino acid proline [6].
• Specific inhibitor studies, using a range of compounds previously untested against a single PE source, indicated that alpha-ketobenzothiazole was the most effective PE inhibitor, with an IC50 value of 41 pM [6].
• Following gel filtration, hydroxylapatite and hydrophobic interaction chromatographies, the prolyl endopeptidase activity was purified 1400-fold with a 23% recovery of activity [7].

Biological context of PREP

• Prolyl oligopeptidase (EC 3.4.21.26, prolyl endopeptidase) cDNA from bovine brain was cloned by PCR, and the amplified fragment was used as a probe to screen the cDNA library from bovine brain [8].
• The amino acid sequence (GMFYNAYPQQDG) of a tryptic peptide from the enzyme is identical to the porcine brain prolyl oligopeptidase sequence 184-195 [9].
• This prolyl endopeptidase activity was shown to have a molecular mass (87 kDa) higher than the cytosolic prolyl endopeptidase but, from initial investigation, appears to demonstrate a similarly broad substrate specificity towards proline-containing neuropeptides [10].
• Thus, Z-Gly-Pro-CHN2 seems to be an active site directed, specific inhibitor of post proline cleaving enzyme [11].
• In the presence of 350 nM Z-Pro-prolinal, a specific inhibitor of prolyl endopeptidase, residual Z-Gly-Pro-NH-Mec hydrolysis of 2.6 U/mg protein was observed [12].

Anatomical context of PREP

• Following vigorous salt washing and osmotic shock, the prolyl endopeptidase activity was released from the membranes by treatment with the detergent Triton X-100, and was partially purified by gel filtration on a Sephacryl S-200HR column [10].
• Prolyl endopeptidase from bovine testis: purification, characterization and comparison with the enzymes from other tissues [13].
• All virus-exposed animals developed fever and showed a significant (P < 0.05, 0.01 or 0.001) drop in the number of circulating leucocytes (neutrophils, lymphocytes and monocytes) by day 3 or 5 post-exposure (PE), which continued to the end of the experiment at day 12 PE [14].
• BVDV was consistently isolated from the peripheral blood buffy coat cells from day 5 PE, and also from selected tissues (spleen, thymus, mesenteric and submaxillary lymph nodes, small intestine, lungs and thyroid gland) that were collected at the time of euthanasia of the animals at day 12 PE [14].

Associations of PREP with chemical compounds

• This residual activity was resistant to inhibition by Z-Pro-prolinal at concentrations in excess of 200 times its reported Ki value for prolyl endopeptidase and could not be inhibited under conditions of prolonged incubation with the inhibitor [12].
• Specific inhibition of post proline cleaving enzyme by benzyloxycarbonyl-Gly-Pro-diazomethyl ketone [11].
• Cleavage of substance P to an N-terminal tetrapeptide and a C-terminal heptapeptide by a post-proline Cleaving enzyme from bovine brain [15].
• The former activity is similar, if not identical to, the post-proline cleaving enzyme in kidney as it is active toward the post-proline cleaving enzyme substrate CbzGly--Pro--Leu--Gly and inhibited by CbzPro--Phe and diisopropylfluorophosphate [16].
• Prolyl endopeptidase, which has long been recognised for its importance in the degradation of several neuropeptides such as thyroliberin, luteinising hormone releasing hormone, angiotensin, substance P and neurotensin, has been widely characterised as a cytosolic enzyme [10].

Analytical, diagnostic and therapeutic context of PREP

• The bovine brain prolyl endopeptidase-encoding cDNA was expressed using an expression vector bearing a tac promoter, with an approximate yield of 20 micrograms/ml of cell culture [8].
• Prolyl oligopeptidase (EC 3.4.21.26) has been purified 26,000-fold from bovine lens tissue by anion-exchange chromatography, gel filtration and isoelectric focussing, with an overall yield of 11% [9].
• Finally, a significant (P < 0.05 or 0.01) enhanced phagocytic capability of the PBMCs, as analyzed by flow cytometry, was observed in virus-exposed animals at days 3, 5, 7, 10 and 12 PE, when compared to control calves [14].
• Lyophilization of Dounce and Mourtzikos beef liver catalase (Prep. Biochem. 11 (1981) 501-523) under specified conditions produced conformationally altered but not completely denatured catalase monomer which retained both significant catalatic activity and peroxidatic activity towards ethanol [17].

References