scholarly journals Oxidized Substrates of APEH as a Tool to Study the Endoprotease Activity of the Enzyme

2021 ◽  
Vol 23 (1) ◽  
pp. 443
Author(s):  
Annamaria Sandomenico ◽  
Marta Gogliettino ◽  
Emanuela Iaccarino ◽  
Carmela Fusco ◽  
Andrea Caporale ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Serine Protease ◽  
Protein Oxidation ◽  
Crucial Role ◽  
Critical Role ◽  
Prolyl Oligopeptidase ◽  
Important Prerequisite ◽  
Endopeptidase Activity

APEH is a ubiquitous and cytosolic serine protease belonging to the prolyl oligopeptidase (POP) family, playing a critical role in the processes of degradation of proteins through both exo- and endopeptidase events. Endopeptidase activity has been associated with protein oxidation; however, the actual mechanisms have yet to be elucidated. We show that a synthetic fragment of GDF11 spanning the region 48–64 acquires sensitivity to the endopeptidase activity of APEH only when the methionines are transformed into the corresponding sulphoxide derivatives. The data suggest that the presence of sulphoxide-modified methionines is an important prerequisite for the substrates to be processed by APEH and that the residue is crucial for switching the enzyme activity from exo- to endoprotease. The cleavage occurs on residues placed on the C-terminal side of Met(O), with an efficiency depending on the methionine adjacent residues, which thereby may play a crucial role in driving and modulating APEH endoprotease activity.

911 The enzyme activity and activation of the serine protease, neuropsin

1996 ◽  
Vol 25 ◽  
pp. S101
Author(s):  
Katsutoshi Sakurai ◽  
Chigusa Shimizu ◽  
Yoshiharu Momota ◽  
Shigetaka Yoshida ◽  
Sadao Shiosaka
Keyword(s):  
Enzyme Activity ◽  
Serine Protease

scholarly journals A molecular mechanism of mouse placental spongiotrophoblast differentiation regulated by prolyl oligopeptidase

Zygote ◽  
2019 ◽  
Vol 27 (1) ◽  
pp. 49-53
Author(s):  
Yuki Maruyama ◽  
Atsushi P. Kimura
Keyword(s):  
Molecular Mechanism ◽  
Critical Role ◽  
Specific Inhibitor ◽  
Cell Types ◽  
Giant Cells ◽  
Akt Pathway ◽  
Prolyl Oligopeptidase ◽  
Trophoblast Stem ◽  
Trophoblast Stem Cell ◽  
Trophoblast Giant Cells

SummaryIn eutherian mammals, the placenta plays a critical role in embryo development by supplying nutrients and hormones and mediating interaction with the mother. To establish the fine connection between mother and embryo, the placenta needs to be formed normally, but the mechanism of placental differentiation is not fully understood. We previously revealed that mouse prolyl oligopeptidase (POP) plays a role in trophoblast stem cell (TSC) differentiation into two placental cell types, spongiotrophoblasts (SpT) and trophoblast giant cells. Here, we focused on SpT differentiation and attempted to elucidate a molecular mechanism. ForAscl2,Arnt, andEgfrgenes that are indispensable for SpT formation, we found that a POP-specific inhibitor, SUAM-14746, significantly decreasedAscl2expression, which was consistent with a significant decrease in expression ofFlt1, a gene downstream ofAscl2. Although this downregulation was unlikely to be mediated by the PI3K-Akt pathway, our results indicated that POP controls TSC differentiation into SpT by regulating theAscl2gene.

scholarly journals Critical role of spectrin in hearing development and deafness

2019 ◽  
Vol 5 (4) ◽  
pp. eaav7803 ◽  
Author(s):  
Yan Liu ◽  
Jieyu Qi ◽  
Xin Chen ◽  
Mingliang Tang ◽  
Cenfeng Chu ◽  
...  
Keyword(s):  
Hair Cells ◽  
Knockout Mice ◽  
Crucial Role ◽  
Structural Organization ◽  
Critical Role ◽  
Super Resolution ◽  
Mechanical Vibrations ◽  
Hearing Ability ◽  
Profound Deafness

Inner ear hair cells (HCs) detect sound through the deflection of mechanosensory stereocilia. Stereocilia are inserted into the cuticular plate of HCs by parallel actin rootlets, where they convert sound-induced mechanical vibrations into electrical signals. The molecules that support these rootlets and enable them to withstand constant mechanical stresses underpin our ability to hear. However, the structures of these molecules have remained unknown. We hypothesized that αII- and βII-spectrin subunits fulfill this role, and investigated their structural organization in rodent HCs. Using super-resolution fluorescence imaging, we found that spectrin formed ring-like structures around the base of stereocilia rootlets. These spectrin rings were associated with the hearing ability of mice. Further, HC-specific, βII-spectrin knockout mice displayed profound deafness. Overall, our work has identified and characterized structures of spectrin that play a crucial role in mammalian hearing development.

scholarly journals Stability of cellulase in ionic liquids: correlations between enzyme activity and COSMO-RS descriptors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jacob Nedergaard Pedersen ◽  
Bianca Pérez ◽  
Zheng Guo
Keyword(s):  
Hydrogen Bond ◽  
Enzyme Activity ◽  
Ionic Liquids ◽  
Bond Energy ◽  
Crucial Role ◽  
Enzymatic Saccharification ◽  
Cellulase Activity ◽  
Cellulose Dissolution ◽  
Ion Size ◽  
Selection Of

AbstractIonic liquids (ILs) are effective in pretreating cellulose for enhanced enzymatic saccharification, however ILs can inactivate cellulases. To guide the selection of ILs, the activity of cellulase was correlated with COSMO-RS calculations and descriptors of ILs including hydrogen bond (H-bond) basicity/acidity, polarity and ion size. Trends were deduced using an anion-series and a cation-series of ionic liquids in aqueous solutions. The activity in the cation-series was best correlated with the size of varied cations, whereas the activity in the anion-series showed a pronounced correlation to H-bond basicity and polarity of different anions. COSMO-RS was further used to predict the solubility of cellulose in ILs, which was correlated with cellulase activity on IL-pretreated cellulose. The best correlations were found between the enzyme activity in the anion-series ILs and the logarithmic activity coefficients, the H-bond energy, H-bond basicity and polarizability, underlining that the anion plays a crucial role in cellulose dissolution.

Possible long-lasting inhibition of converting enzyme by enalapril in human cerebrospinal fluid

1993 ◽  
Vol 84 (3) ◽  
pp. 313-317 ◽  
Author(s):  
Marcello Fanciullacci ◽  
Massimo Alessandri ◽  
Maria Nicolodi ◽  
Sergio Michelacci ◽  
Federigo Sicuteri
Keyword(s):  
Cerebrospinal Fluid ◽  
Enzyme Activity ◽  
Oral Dose ◽  
Neutral Endopeptidase ◽  
The Other ◽  
Clinical Effects ◽  
Converting Enzyme ◽  
Human Cerebrospinal Fluid ◽  
Opioid Mechanisms ◽  
Endopeptidase Activity

1. Converting enzyme and neutral endopeptidase activities were both measured every 3 h by a fluorimetric method in plasma and cerebrospinal fluid of patients diagnosed as migraineurs with aura after lumbar puncture, which was performed 9 h after an acute oral dose of enalapril or placebo. 2. A reduced converting enzyme activity, as compared with placebo, was observed in patients who were given enalapril. On the other hand, neutral endopeptidase activity detected after enalapril did not differ from that measured after placebo. 3. The results seem to indicate that enalapril penetrates the blood-brain barrier in sufficient amounts to reduce converting enzyme activity. Moreover, neutral endopeptidase was not affected by enalapril. Therefore, those clinical effects of the drug which have been attributed to the involvement of central opioid mechanisms may depend on the inhibition of brain converting enzyme but not the inhibition of brain neutral endopeptidase.

scholarly journals Benzyloxycarbonylprolylprolinal, a transition-state analogue for prolyl oligopeptidase, forms a tetrahedral adduct with catalytic serine, not a reactive cysteine

1997 ◽  
Vol 322 (3) ◽  
pp. 839-843 ◽  
Author(s):  
Ara KAHYAOGLU ◽  
Khadijeh HAGHJOO ◽  
Ferenc KRAICSOVITS ◽  
Frank JORDAN ◽  
Laszlo POLGAR
Keyword(s):  
Chemical Shift ◽  
Chemical Modification ◽  
Transition State ◽  
Molecular Mass ◽  
Serine Protease ◽  
13C Nmr ◽  
Dimethyl Sulphoxide ◽  
Tetrahedral Complex ◽  
Prolyl Oligopeptidase ◽  
Transition State Analogue

N-Benzyloxycarbonyl-l-prolyl-l-[1-13C]prolinal was synthesized starting with reduction of l-[1-13C]Pro to l-[1-13C]prolinol, followed by coupling with N-benzyloxycarbonyl-l-Pro to N-benzyloxycarbonyl-l-Pro-l-[1-13C]prolinol (Z-Pro-[1-13C]prolinol), and finally oxidation of the alcohol to the aldehyde with dimethyl sulphoxide. While the 13C NMR chemical shift of the aldehyde carbon is 202 p.p.m., that of the aldehyde hydrate is between 91.6 and 91.8 p.p.m., that of the dithiothreitol adduct is between 74.8 and 75.0 p.p.m., and that in the presence of the serine protease prolyl oligopeptidase is at 92.3 p.p.m.. The linewidth of the latter is 114 Hz, roughly consistent with the molecular mass of 80 kDa reported for the enzyme. Inverse detection experiments gave a 1H resonance at 5.29 p.p.m. with a linewidth of 80 Hz, also consistent with the expected chemical shift and linewidth for a hemiacetal bound to such a large enzyme, while the free hydrate gave resonances at 5.18 and 5.25 p.p.m., with very much narrower linewidths. It is concluded that Z-Pro-prolinal, a putative transition-state analogue for prolyl oligopeptidase, forms a tetrahedral complex with the enzyme at its catalytic serine, rather than at a neighbouring cysteine that was found to be highly reactive according to chemical modification studies.

scholarly journals Modeling Adipogenesis: Current and Future Perspective

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2326 ◽  
Author(s):  
Hisham F. Bahmad ◽  
Reem Daouk ◽  
Joseph Azar ◽  
Jiranuwat Sapudom ◽  
Jeremy C. M. Teo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Crucial Role ◽  
Critical Role ◽  
Treatment Modalities ◽  
Future Perspective ◽  
Adipose Derived Stem Cells ◽  
Physiological Importance ◽  
And Personalized Medicine

Adipose tissue is contemplated as a dynamic organ that plays key roles in the human body. Adipogenesis is the process by which adipocytes develop from adipose-derived stem cells to form the adipose tissue. Adipose-derived stem cells’ differentiation serves well beyond the simple goal of producing new adipocytes. Indeed, with the current immense biotechnological advances, the most critical role of adipose-derived stem cells remains their tremendous potential in the field of regenerative medicine. This review focuses on examining the physiological importance of adipogenesis, the current approaches that are employed to model this tightly controlled phenomenon, and the crucial role of adipogenesis in elucidating the pathophysiology and potential treatment modalities of human diseases. The future of adipogenesis is centered around its crucial role in regenerative and personalized medicine.

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