The Laboratory of Peptide Research with Dr. Ervin G. Erdös as Director, has been studying enzymes that activate, inactivate or modulate the actions of vaso- and neuro-active peptides. The contributions of this laboratory include:
The discovery, purification and cloning of human plasma carboxypeptidase N, (kininase I) that inactivates kinins, anaphylatoxins and other peptides and proteins;
The discovery of kininase II in the kidney and human blood, and proving that this enzyme is identical with the angiotensin I converting enzyme. Inhibitors are currently used in clinical practice to treat millions of patients suffering from high blood pressure or congestive heart failure;
The discovery of cell membrane-bound carboxypeptidase M, which activates, inactivates or modulates the actions of prohormones and peptides;
The discovery, purification and cloning of prolylcarboxypeptidase (angiotensinase C), a new type of serine peptidase, protease.
Some of these enzymes were expressed in a variety of systems as recombinant proteins and employed to elicit antibodies.Recently, we are co-expressing peptide receptors and peptidases in cultured cells. The crystal structure of human carboxypeptidase N will be determined as a cooperative venture with the Max Planck Institute in Munich. Cultured kidney cells were transfected with kallikrein DNA to study the activation, glycosylation and release of this enzyme into the medium.
Research was directed also to determine the complete amino acid sequence, biogenesis and distribution of a truncated, smaller version of the human angiotensin I converting enzyme, representing a single active domain only.
We are studying the differences in substrate specificity and inhibition pattern between the two active sites on the N-and C-domains of human converting enzyme. We are also investigating the interaction of receptor proteins with enzyme. We are also investigating the interaction of receptor proteins with enzymes on the plasma membrane, the mode of potentiating kinin effect on the receptor with peptidase inhibitorsi.
Selected Publications (out of 370 published):
1. Jackman, H.L., Morris, P.W., Deddish, P.A., Skidgel, R.A., Erdös, E.G.: J. Biol. Chem. 267:2872-2875, 1992.
2. Tan, F., Morris, P.W., Skidgel, R.A., and Erdös, E.G., : Sequencing and cloning of human prolylcarboxypeptidase (angiotensinase C): Similarity to both serine carboxypeptidase and prolylendopeptidase families. J. Biol. Chem. 268: 16631-16638, 1993.
3. Dragovic, T., Deddish, P.A., Tan, F., Weber, G. and Erdös, E.G. : Increased expression of neprilysin (neutral endopeptidase 24.11) in rat and human hepatocellular carcinomas. Lab. Invest. 70: 107-113, 1994.
4. Deddish, P.A., Wang, J., Michel, B., Morris, P.W., Davidson, N.O., Skidgel, R.A., Erdös, E.G.: Naturally occurring active N -Domain of human angiotensi I converting enzyme.Proc. Natl. Acad. Sci. USA.91:7807-7811, 1994
5.Jackman, H.L., Tan, F., Schraufnagel, D., Dragovic, T. Dezsös, B., Becker, R.P., and Erdös, E.G.: Plasma membrane-bound and lysosomal peptidases in human alveolar macrophages. Am. J. Respir. Cell Mol. Biol. 13:196-204, 1995.
6.Abe, M., Nakamura, F. Tan, F., Deddish, P.A., Colley, K.J., Becker, R.P., Skidgel, R.A,. and Erdös, E.G.:: Expression of rat kallikrein and the epithelil polarity in transfected Madin-Darby canine kidney cells.Hypertension 26:891-898, 1995.
7.Michel, B., Igic, R., Leray, V., Deddish, P.A., and Erdös, E.G.: Removal of Arg141 from the a chain of human hemoglobin by carboxypeptidase N and M.Circul. Res. 78:635-642, 1996.
8.Deddish, P.A., Wang,L.-X., Jackman, H.L., Michel, B., Wang, J., Skidgel, R.A., and Erdös, E.G.: Single-domain angiotensin I converting enzyme (kininase II; ACE): Characterization and properties .J. Pharmacol. Exp. Therap. 279:1582-1589. 1996.
9.Deddish, P.A., Jackman, H.L., Skidge, R.A., Erdös, E.G. Differences in the hydrolysis of enkephalin congeners by the two domains of angiotensin converting emzyme.Biochem. Pharmacol.(In Press).
E-mail EGErdos@uic.edu