Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proline requirement of Salmonella typhimurium strain proB25 can be satisfied by either of the peptides Leu-Pro or Gly-Pro-Ala. A mutant derivative of strain proB25 isolated by penicillin selection in medium containing Leu-Pro as proline source fails to use either Leu-Pro or Gly-Pro-Ala as a source of proline. This strain is a double mutant that lacks two aminoacyl-proline-specific peptidases. One of these enzymes (peptidase Q) catalyzes the rapid hydrolysis of Leu-Pro but does not hydrolyze Gly-Pro-Ala or poly-l-proline. Mutations at a site (pepQ) near metE lead to loss of this activity. The other peptidase (peptidase P) catalyzes the hydrolysis of Gly-Pro-Ala and poly-l-proline but is only weakly active with Leu-Pro as substrate. This enzyme is similar to aminopeptidase P previously described in Escherichia coli (16). Mutations at a locus (pepP) near serA lead to loss of this enzyme.
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PMID:Isolation and characterization of proline peptidase mutants of Salmonella typhimurium. 460 25

An enzyme present in mouse brain cytosol cleaves C-terminal dipeptides from substrates including ACTH-(7-10) (Phe-Arg-Trp-Gly), and des-Tyr-[Met]- and des-Tyr-[Leu]enkephalin. By means of ion-exchange chromatography and gel filtration, the peptidase was purified to a specific activity of 1570 times that of brain homogenate. At this purification, a second peptidase, which hydrolyzes Trp-Gly and other peptides [M. E. A. Reith and A. Neidle (1979) Biochem. Biophys. Res. Commun. 90, 794-800] was still present, but could be removed by preparative polyacrylamide gel electrophoresis. The des Tyr-enkephalin-cleaving enzyme has a molecular weight of about 85,000 and a pH optimum of 7.8. It is inhibited by metal-chelating and sulfhydryl reagents. The enzyme has a strong preference for substrates with an aromatic residue in the position adjacent to the C-terminal amino acid, although some peptides meeting this criterion were competitive inhibitors rather than substrates. Peptides with less than four residues were inactive and, in general, tetrapeptides were found to be more reactive than larger analogs, when peptides with common C-terminal sequences were compared. The peptidyl dipeptidase, which has not been described previously, can be readily distinguished from angiotensin-converting enzyme (EC 3.4.15.1) and from neutral endopeptidase (EC 3.4.24.11) by its subcellular localization, substrate specificity, and response to inhibitors. It was suggested that peptidyl dipeptidase-B (PDP-B, EC 3.4.15.-) would be an appropriate name for the enzyme. PDP-B is widely distributed among mouse tissues.
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PMID:The isolation of a peptidyl dipeptidase from mouse brain cytosol that cleaves adrenocorticotropic hormone-(7-10) and des-tyrosine-enkephalins. 608 38

The role of each enkephalin-hydrolyzing peptidase in the inhibitory potency of exogenously added enkephalins in the myenteric plexus-longitudinal muscle preparation of guinea-pig ileum was studied by using the relatively specific inhibitor of each enzyme. Results showed that three distinct enzymes, bestatin-sensitive aminopeptidase(s), angiotensin converting enzyme, and thiorphan-sensitive "enkephalinase", played a critical role in the inactivation of enkephalins. Additionally, these enzymes are likely to be located close to opioid receptors, since they produce a significant concentration difference of enkephalin between the surrounding organ bath and the vicinity of opioid receptors. In contrast to these three enzymes, both L-tyrosyl-L-tyrosine-sensitive dipeptidyl aminopeptidase and D-phenylalanine-sensitive carboxypeptidase are indicated not to be involved significantly in the degradation of exogenously added enkephalins in the guinea-pig ileum.
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PMID:The role of bestatin-sensitive aminopeptidase, angiotensin converting enzyme and thiorphan-sensitive "enkephalinase" in the potency of enkephalins in the guinea-pig ileum. 609 2

Antisera raised against specific renal brush border peptidases have been used to characterize vascular surface membrane angiotensin I converting enzyme (ACE; EC 3.4.15.1), aminopeptidase M (AmM; EC 3.4.11.2), and dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) by techniques of differential solubilization, fused-rocket immunoelectrophoresis and crossed immunoelectrophoresis. The vascular membrane-bound enzymes are immunologically indistinguishable from their brush border counterparts and can be solubilized by treatment with detergent and/or papain. The electrophoretic mobilities of the papain-treated forms of each enzyme were greater than those of the detergent-treated forms. This increased mobility is associated with the removal of small, hydrophobic, non-antigenic components of the enzymes. Regardless of the method of solubilization, the electrophoretic mobilities of the vascular enzymes were greater than those of the brush border enzymes. However, after treatment with neuraminidase to remove sialic acid, their respective mobilities were similar. The mobilities of serum AmM and DAP IV were identical to the respective papain-solubilized vascular enzymes both before and after neuraminidase. Thus, like the brush border enzymes, the data presented are consistent with the model that vascular ACE, AmM and DAP IV are intrinsic membrane peptidases bound to their surface membranes by small, non-antigenic, hydrophobic anchors associated with the lipid bilayer. In addition, these vascular surface membrane peptidases are similar to and may be a source of the circulating enzymes.
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PMID:Immunoelectrophoretic analysis of vascular, membrane-bound angiotensin I converting enzyme, aminopeptidase M, and dipeptidyl(amino)peptidase IV. 614 48

Using a preparation for the perfusion of the subarachnoidal spaces of the spinal cord of rats it was found that substance P can stimulate the release of YGGFMRF and YGGFM. We have studied the effect of several peptidase inhibitors (captopril, bestatin, thiorphan) on the recovery of YGGFMRF and YGGFM released from spinal cord by substance P. The recovery of released YGGFMRF was increased by adding captopril to the perfusion medium. A combination of captopril and bestatin in the perfusion medium further increases this YGGFMRF recovery. Intrathecal injection of captopril and bestatin also potentiated the analgesic effect of YGGFMRF and electroacupuncture. These results suggest that substance P may act as a "releaser" of enkephalins in spinal cord and that the dipeptidyl carboxypeptidase and aminopeptidase may be important in the degradation of YGGFMRF in vivo.
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PMID:The effect of peptidase inhibitors on the release of Met5-Enk-Arg6-Phe7 (YGGFMRF) and Met5-enkephalin (YGGFM) from spinal cord induced by substance P in vivo. 619 74

In the spinal cord Met5-enkephalin-Arg6-Phe7 (YGGFMRF) is located in small interneurons of the dorsal and ventral horns. From these storage sites, YGGFMRF can be released by perfusing the subarachnoidal spaces of the spinal cord with artificial spinal fluid containing substance P. In vitro YGGFMRF can be hydrolyzed readily by a dipeptidyl carboxypeptidase. In order to ascertain whether this reaction is physiologically relevant, we measured the content of YGGFMRF and Met5-enkephalin (YGGFM) in subarachnoidal space perfusate in presence and in absence of captopril, bestatin and thiorphan using substance P to activate the release of opioid peptides. Without peptidase inhibitors, the efflux of YGGFMRF and YGGFM was hardly detectable. The addition of captopril to the perfusion medium increased the substance P (10(-7) M)-induced release of YGGFMRF markedly but it increased the efflux of YGGFM to a much smaller extent. When captopril and bestatin were added together the amount of YGGFMRF present in the perfusate was further increased slightly. In contrast, the YGGFM content in the same perfusate was increased greatly by bestatin and only slightly by thiorphan. To characterize the pharmacological profile of these peptidase inhibitors, we compared electroacupuncture antinociception with and without intrathecal injections of captopril and bestatin. This antinociception, as measured by tail-flick latency, was potentiated by the intrathecal injection of captopril and bestatin. These results taken together suggest that YGGFMRF released in the perfusate of the arachnoidal space by substance P is metabolized by both dipeptidyl carboxypeptidase and aminopeptidase.
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PMID:Action of peptidase inhibitors on methionine5-enkephalin-arginine6-phenylalanine7 (YGGFMRF) and methionine5-enkephalin (YGGFM) metabolism and on electroacupuncture antinociception. 620 38

The degradation of des-Arg9-brady kinin and its analogues by highly purified preparations of hog lung and kidney kininase II (angiotensin-converting enzyme; peptidyldipeptide hydrolase, EC 3.4.15.1) was studied. The degradative peptides fragments were separated and isolated by high performance liquid chromatography and identified by amino acid analysis. Both enzymes released C-terminal tripeptides from des-Arg9-bradykinin, des-Arg9-(Leu8)-bradykinin, Pro-Pro-Gly-Phe-Ser-Pro-Phe, Pro-Gly-Phe-Ser-Pro-Phe, Gly-Phe-Ser-Pro-Phe, Bz-Gly-Ser-pro-Phe and Bz-Gly-Ala-Pro-Phe. Hydrolysis of Phe-Ser-Pro-Phe, Bz-Gly-His-Pro-Phe, Bz-Gly-Phe-Pro-Phe and Bz-Gly-Gly-Pro-Phe by both enzymes was negligible. These data indicate that kininase II can release C-terminal tripeptides of substrates having a proline residue in the penultimate position such as des-Arg9-bradykinin and its analogues, and that this enzyme is able not only to act as a dipeptidyl carboxypeptidase but also acts as a tripeptidyl carboxy-peptidase. The tripeptidyl carboxypeptidase enzyme was sensitive to inhibition by kininase II inhibitors.
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PMID:Tripeptidyl carboxypeptidase activity of kininase II (angiotensin-converting enzyme). 627 13

Angiotensin I converting enzyme (kininase II, peptidyl dipeptidase, ACE) was purified by reverse immunoadsorption from a membrane fraction of the human kidney. ACE is very likely a transmembrane peptidase. Treatment of the membrane-bound enzyme with trypsin releases a low mol. wt. fragment (greater than 10,000), which is probably the anchor peptide inserted into the plasma membrane. Antibody to ACE was used to localize it in the CNS where it is bound to plasma membrane of neuroepithelial cells in structures such as the globus pallidus or substantia nigra. Radioimmunoassay indicated that ACEs of endothelial, epithelial and neuroepithelial origin are immunologically identical. Direct radioimmunoassay also showed that there is a strong negative correlation between plasma enzyme level and pulmonary diffusing capacity of sarcoid patients. Finally, in addition to various peptides, homogeneous human ACE cleaves fluorogenic substrates where the C-terminal amino acid is replaced with nitrobenzylamine.
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PMID:Human converting enzyme. 631 67

A mutant strain of Salmonella typhimurium that lacks two proline-specific peptidases (peptidases P and Q) could not complete the degradation of proline peptides formed as intermediates in starvation-induced protein breakdown. The wild-type strain produced free proline as the product of degradation of proline-labeled proteins. The pepP pepQ mutant, however, produced a mixture of small proline peptides. In the absence of peptidase Q only, peptidase P could complete the degradation of most of the proline peptide intermediates formed. In the absence of peptidase P only, about 50% of the proline-labeled, acid-soluble products were proline peptides. These results are consistent with in vitro specificity data indicating that peptidase Q hydrolyzes X-Pro dipeptides only, whereas peptidase P attacks both X-Pro dipeptides and longer peptides with X-Pro at their N-termini. A mutant strain lacking four broad-specificity peptidases (peptidases N, A, B, and D), but containing peptidases P and Q, also produced proline peptides as products of protein breakdown. This observation suggests that broad-specificity peptidases are required to generate the X-Pro substrates of peptidases P and Q. A strain lacking six peptidases (N, A, B, D, P, and Q) was constructed and produced less free proline from protein breakdown than either the pepP pepQ strain or the pepN pepA pepB pepD strain. These observations suggest that the degradation of peptide intermediates involves the sequential removal of N-terminal amino acids and requires both broad-specificity aminopeptidases (peptidases N, A, and B) and the X-Pro-specific aminopeptidase, peptidase P.
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PMID:Degradation of proline peptides in peptidase-deficient strains of Salmonella typhimurium. 633 37

Mutants of Salmonella typhimurium deficient in dipeptidyl carboxypeptidase have been isolated by screening for clones unable to use N-acetyl-L-alanyl-L-alanyl-L-alanine (AcAla3) as the sole nitrogen source. An insertion of the transposable element Tn10 near dcp (the locus coding for dipeptidyl carboxypeptidase) has been isolated and used to map the locus in the interval between purB and trp, an otherwise genetically silent region of the S. typhimurium map. All dcp mutants could still grow using N-acetyl-L-alanyl-L-alanyl-L-alanyl-L-alanine (AcAla4) as the sole nitrogen source. Crude extracts from the dcp mutants failed to hydrolyze AcAla3 but retained approximately 80% of the wild-type activity toward AcAla4. Several lines of evidence indicate that hydrolysis of AcAla4 in the dcp mutant results from the action of a new peptidase distinct from dipeptidyl carboxypeptidase. A mutant strain lacking dipeptidyl carboxypeptidase in addition to peptidases N, A, B, and D showed reduced protein breakdown during carbon starvation compared with a strain lacking only peptidases N, A, B, and D.
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PMID:Dipeptidyl carboxypeptidase-deficient mutants of Salmonella typhimurium. 633 91


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