scholarly journals Identification and properties of a peptidyl dipeptidase in the housefly, Musca domestica, that resembles mammalian angiotensin-converting enzyme

1994 ◽  
Vol 299 (3) ◽  
pp. 651-657 ◽  
Author(s):  
N S Lamango ◽  
R E Isaac
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Musca Domestica ◽  
Gel Filtration ◽  
Converting Enzyme ◽  
Ph Optimum ◽  
Somatic Tissues ◽  
Ic50 Values ◽  
Bivalent Metal Ions ◽  
Membrane Bound ◽  
Dipeptidase Activity

[D-Ala2,Leu5]Enkephalin was readily metabolized by membranes (40,000 g pellet) prepared from heads of the housefly, Musca domestica, with Gly3-Phe4 being the major site of cleavage. This hydrolysis was only partially inhibited (40%) by 10 microM phosphoramidon, an inhibitor of endopeptidase-24.11, but was almost totally abolished in the presence of a mixture of 10 microM phosphoramidon and 10 microM captopril, a potent inhibitor of mammalian angiotensin-converting enzyme (ACE). An assay for ACE employing Bz-Gly-His-Leu as the substrate was used to confirm the presence of an ACE-like peptidyl dipeptidase activity in fly head membranes. The peptidase had a Km of 1.91 mM for Bz-Gly-His-Leu and a pH optimum of 8.2. The activity was inhibited by 100 microM EDTA and was greatly activated by ZnCl2 but not other bivalent metal ions. Captopril, lisinopril, fosinoprilat and enalaprilat, all selective inhibitors of mammalian ACE, were also good inhibitors of the insect enzyme with IC50 values of 400 nM, 130 nM, 16 nM and 290 nM respectively. An M(r) value of around 87,000 was obtained for this enzyme from gel-filtration chromatography, indicating that the insect enzyme is similar in size to mammalian testicular ACE (M(r) = 90,000-110,000) and not the larger form of the enzyme (M(r) = 150,000-180,000) found in mammalian somatic tissues. The fly peptidyl dipeptidase was released from membranes into a soluble fraction by incubating the head membranes at 37 degrees C but not at 0 degree C, suggesting that the insect ACE-like enzyme can be solubilized from cell surfaces through the activity of a membrane-bound enzyme activity. In conclusion, we have shown the existence of a peptidyl dipeptidase in membranes from the heads of M. domestica, which has similar properties to those of mammalian ACE.

scholarly journals Characterization of a secretase activity which releases angiotensin-converting enzyme from the membrane

1993 ◽  
Vol 292 (2) ◽  
pp. 597-603 ◽  
Author(s):  
S Y Oppong ◽  
N M Hooper
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Human Kidney ◽  
Soluble Form ◽  
Converting Enzyme ◽  
Ph Optimum ◽  
Secretase Activity ◽  
Sds Page ◽  
Microsomal Membranes ◽  
Membrane Bound ◽  
Triton X

Angiotensin-converting enzyme (ACE; EC 3.4.1.15.1) exists in both membrane-bound and soluble forms. Phase separation in Triton X-114 and a competitive e.l.i.s.a. have been employed to characterize the activity which post-translationally converts the amphipathic, membrane-bound form of ACE in pig kidney microvilli into a hydrophilic, soluble form. This secretase activity was enriched to a similar extent as other microvillar membrane proteins, was tightly membrane-associated, being resistant to extensive washing of the microvillar membranes with 0.5 M NaCl, and displayed a pH optimum of 8.4. The ACE secretase was not affected by inhibitors of serine-, thiol- or aspartic-proteases, nor by reducing agents or alpha 2-macroglobulin. The metal chelators, EDTA and 1,10-phenanthroline, inhibited the secretase activity, with, in the case of EDTA, an inhibitor concentration of 2.5 mM causing 50% inhibition. In contrast, EGTA inhibited the secretase by a maximum of 15% at a concentration of 10 mM. The inhibition of EDTA was reactivated substantially (83%) by Mg2+ ions, and partially (34% and 29%) by Zn2+ and Mn2+ ions respectively. This EDTA-sensitive secretase activity was also present in microsomal membranes prepared from pig lung and testis, and from human lung and placenta, but was absent from human kidney and human and pig intestinal brush-border membranes. The form of ACE released from the microvillar membrane by the secretase co-migrated on SDS/PAGE with ACE purified from pig plasma, thus the action and location of the secretase would be consistent with it possibly having a role in the post-translational proteolytic cleavage of membrane-bound ACE to generate the soluble form found in blood, amniotic fluid, seminal plasma and other body fluids.

scholarly journals Regulated cleavage-secretion of the membrane-bound angiotensin-converting enzyme.

1994 ◽  
Vol 269 (3) ◽  
pp. 2125-2130
Author(s):  
R. Ramchandran ◽  
G.C. Sen ◽  
K. Misono ◽  
I. Sen
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Membrane Bound

scholarly journals Geospallins A–C: New Thiodiketopiperazines with Inhibitory Activity against Angiotensin-Converting Enzyme from a Deep-Sea-Derived Fungus Geosmithia pallida FS140

Marine Drugs ◽  
2018 ◽  
Vol 16 (12) ◽  
pp. 464 ◽  
Author(s):  
Zhang-Hua Sun ◽  
Jiangyong Gu ◽  
Wei Ye ◽  
Liang-Xi Wen ◽  
Qi-Bin Lin ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Inhibitory Activity ◽  
Deep Sea ◽  
Electrospray Mass Spectrometry ◽  
Hydroxyl Group ◽  
Converting Enzyme ◽  
Deep Sea Sediment ◽  
Spectroscopic Analyses ◽  
Ic50 Values ◽  
Tertiary Hydroxyl

Three new thiodiketopiperazines, geospallins A–C (1–3), together with nine known analogues (4–12), were isolated from the culture of the deep-sea sediment-derived fungus Geosmithia pallida FS140. Among them, geospallins A and B (1 and 2) represent rare examples of thiodiketopiperazines featuring an S-methyl group at C-10 and a tertiary hydroxyl group at C-11. Their structures were determined by high-resolution electrospray mass spectrometry (HRESIMS), spectroscopic analyses, and electronic circular dichroism (ECD) calculations. Their angiotensin-converting enzyme (ACE) inhibitory activity was reported, and geospallins A–C (1–3) showed inhibitory activity with IC50 values of 29–35 µM.

scholarly journals Purification and properties of the enzyme arylamine N-acetyltransferase from the housefly Musca domestica

1993 ◽  
Vol 295 (1) ◽  
pp. 149-154 ◽  
Author(s):  
D P Whitaker ◽  
M W Goosey
Keyword(s):  
Musca Domestica ◽  
Gel Filtration ◽  
Potassium Phosphate ◽  
Acetyl Coa ◽  
Ph Optimum ◽  
A Value ◽  
Purification And Properties ◽  
Sds Page ◽  
Mammalian Enzyme ◽  
Monomeric Structure

The enzyme arylamine N-acetyltransferase (ANAT) from the housefly (Musca domestica) has been purified. The M(r) of the purified enzyme was 27,600 +/- 1700 as estimated by gel filtration. SDS/PAGE yielded a value of 26,000 +/- 300, clearly indicating a monomeric structure. The purified enzyme had apparent Km values for acetyl-CoA and tyramine of 8.4 microM and 8.8 microM respectively, a pH optimum of 7.2 in 10 mM potassium phosphate buffer and an apparent pI of 5.8. ANAT activity showed a strong dependency on the presence of 2-mercaptoethanol during the purification stages. The enzyme could be completely inactivated by treatment with p-chloromercuribenzoate although the enzyme activity was protected by preincubation with acetyl-CoA. One or more cysteine residues are clearly required for catalytic activity, as demonstrated for the mammalian enzyme. In contrast, partial sequencing of the enzyme has yielded a number of peptide sequences, including the N-terminal sequence, which show no similarity with those reported for the mammalian and avian enzymes.

scholarly journals Angiotensin converting enzyme 2 is a novel target of the γ-secretase complex

2020 ◽  
Author(s):  
Alberto Bartolomé ◽  
Jiani Liang ◽  
Pengfei Wang ◽  
David D. Ho ◽  
Utpal B. Pajvani
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Structural Similarity ◽  
Ectodomain Shedding ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Membrane Bound ◽  
Novel Target ◽  
Functional Receptor

AbstractAngiotensin converting enzyme 2 (ACE2) is a key regulator of the renin-angiotensin system, but also the functional receptor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on structural similarity with other γ-secretase (γS) targets, we hypothesized that ACE2 may be affected by γS proteolytic activity. We found that after ectodomain shedding, ACE2 is targeted for intramembrane proteolysis by γS, releasing a soluble ACE2 C-terminal fragment. Consistently, chemical or genetic inhibition of γS results in the accumulation of a membrane-bound fragment of ectodomain-deficient ACE2. Although chemical inhibition of γS does not alter SARS-CoV-2 cell entry, these data point to a novel pathway for cellular ACE2 trafficking.

scholarly journals Interaction of SARS-CoV-2 and Other Coronavirus With ACE (Angiotensin-Converting Enzyme)-2 as Their Main Receptor

Hypertension ◽  
2020 ◽  
Vol 76 (5) ◽  
pp. 1339-1349 ◽  
Author(s):  
Anne M. Davidson ◽  
Jan Wysocki ◽  
Daniel Batlle
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Scientific Research ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Therapeutic Implications ◽  
Protein Receptor ◽  
Type Ii Pneumocytes ◽  
A Cell ◽  
Membrane Bound ◽  
Novel Coronavirus

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 originated from Wuhan, China, in December 2019 and rapidly spread to other areas worldwide. Since then, coronavirus disease 2019 (COVID-19) has reached pandemic proportions with >570 000 deaths globally by mid-July 2020. The magnitude of the outbreak and the potentially severe clinical course of COVID-19 has led to a burst of scientific research on this novel coronavirus and its host receptor ACE (angiotensin-converting enzyme)-2. ACE2 is a homolog of the ACE that acts on several substrates in the renin-Ang (angiotensin) system. With unprecedented speed, scientific research has solved the structure of SARS-CoV-2 and imaged its binding with the ACE2 receptor. In SARS-CoV-2 infection, the viral S (spike) protein receptor-binding domain binds to ACE2 to enter the host cell. ACE2 expression in the lungs is relatively low, but it is present in type II pneumocytes—a cell type also endowed with TMPRSS2 (transmembrane protease serine 2). This protease is critical for priming the SARS-CoV-2 S protein to complex with ACE2 and enter the cells. Herein, we review the current understanding of the interaction of SARS-CoV-2 with ACE2 as it has rapidly unfolded over the last months. While it should not be assumed that we have a complete picture of SARS-CoV-2 mechanism of infection and its interaction with ACE2, much has been learned with clear therapeutic implications. Potential therapies aimed at intercepting SARS-CoV-2 from reaching the full-length membrane-bound ACE2 receptor using soluble ACE2 protein and other potential approaches are briefly discussed as well.

Separation of Angiotensin-Converting Enzyme Inhibitors from Fermented Milk Prepared with Lactobacillus casei HZ1

2011 ◽  
Vol 345 ◽  
pp. 161-167 ◽  
Author(s):  
Zhao Han ◽  
Xue Gang Luo ◽  
Hua Tian ◽  
Yan Men ◽  
Nan Wang ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Lactobacillus Casei ◽  
Membrane Filtration ◽  
Gel Filtration ◽  
Fermented Milk ◽  
Exchange Chromatography ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Inhibitory Rate ◽  
Ace Inhibitory

In this paper, a strain HZ1 which was isolated in our former works was classified as Lactobacillus Casei (L. Casei) by 16S rDNA sequence analysis. The results of angiotensin-converting enzyme (ACE) inhibitory assay showed that this novel stain was able to produce ACE inhibitory components when it was used to fermented milk. Applying the methods of membrane filtration and anion-exchange chromatography with fast protein liquid chromatography (FPLC) system, nine fractions with remarkable ACE inhibitory activity were obtained, and two bioactive fractions, recorded as ACEI-2 and ACEI-5, exhibited the highest ACE inhibitory rate of 60.55% and 71.71%, respectively. Furthermore, seven fractions proteins/polypeptides, which exhibited ACE inhibitory rate higher than 50% were separated from ACEI-2 and ACEI-5 by using sephadex gel filtration chromatography. These works might provide a foundation for the following study of L. Casei HZ1 and its probiotics functions, and contribute to the development of functional foods or drugs that provide health benefits to patients suffering from hypertension.

Sign in / Sign up

Export Citation Format

Share Document