Angiotensin converting enzyme (ACE) is one of a class of zinc metallopeptidases that catalyze the cleavage of dipeptides from the C-terminal of oligopeptides and proteins. The enzyme from lung plays a central role in blood pressure regulation and lately much attention has been given to the design and use of ACE inhibitors as antihypertensive agents. The enzyme is also present in other tissues where its biological role is unknown. We have recently developed an affinity chromatographic method for ACE that allows us to obtain the enzyme conveniently, in quantities sufficient for physicochemical characterization. We plan to investigate the structural basis for chloride activation, the role of zinc and tyrosine in catalysis, enzymatic reaction intermediates and the putative endopeptidase activity of ACE. We will also examine the dipeptidyl carboxypeptidase from tissues other than lung - expecially testes, heart and brain - and from different species. By identifying physiological substrates for these enzymes we should be able to define their role in processing biologically active peptides.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034704-03
Application #
3347908
Study Section
Physical Biochemistry Study Section (PB)
Project Start
1985-09-01
Project End
1990-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
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Yu, X C; Sturrock, E D; Wu, Z et al. (1997) Identification of N-linked glycosylation sites in human testis angiotensin-converting enzyme and expression of an active deglycosylated form. J Biol Chem 272:3511-9
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Sturrock, E D; Yu, X C; Wu, Z et al. (1996) Assignment of free and disulfide-bonded cysteine residues in testis angiotensin-converting enzyme: functional implications. Biochemistry 35:9560-6
Ehlers, M R; Schwager, S L; Scholle, R R et al. (1996) Proteolytic release of membrane-bound angiotensin-converting enzyme: role of the juxtamembrane stalk sequence. Biochemistry 35:9549-59
Riordan, J F (1995) Angiotensin II: biosynthesis, molecular recognition, and signal transduction. Cell Mol Neurobiol 15:637-51
Ehlers, M R; Scholle, R R; Riordan, J F (1995) Proteolytic release of human angiotensin-converting enzyme expressed in Chinese hamster ovary cells is enhanced by phorbol ester. Biochem Biophys Res Commun 206:541-7
Ehlers, M R; Chen, Y N; Riordan, J F (1991) Spontaneous solubilization of membrane-bound human testis angiotensin-converting enzyme expressed in Chinese hamster ovary cells. Proc Natl Acad Sci U S A 88:1009-13
Ehlers, M R; Chen, Y N; Riordan, J F (1991) Purification and characterization of recombinant human testis angiotensin-converting enzyme expressed in Chinese hamster ovary cells. Protein Expr Purif 2:1-9
Ehlers, M R; Riordan, J F (1991) Angiotensin-converting enzyme: zinc- and inhibitor-binding stoichiometries of the somatic and testis isozymes. Biochemistry 30:7118-26

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