Abstract
Somatic angiotensin-I converting enzyme (sACE) has an essential role in the regulation of blood pressure and electrolyte fluid homeostasis. It is a zinc protease that cleaves angiotensin-I (AngI), bradykinin, and a broad range of other signalling peptides. The enzyme activity is provided by two homologous domains (N- and C-), which display clear differences in substrate specificities and chloride activation. The presence of chloride ions in sACE and its unusual role in activity was identified early on in the characterisation of the enzyme. The molecular mechanisms of chloride activation have been investigated thoroughly through mutagenesis studies and shown to be substrate-dependent. Recent results from X-ray crystallography structural analysis have provided the basis for the intricate interactions between ACE, its substrate and chloride ions. Here we describe the role of chloride ions in human ACE and its physiological consequences. Insights into the chloride activation of the N- and C-domains could impact the design of improved domain-specific ACE inhibitors.
About the authors
Geoffrey Masuyer obtained is PhD in Structural Biology at the University of Bath in 2011. Since then he has worked as a post-doctoral research associate with Prof. K. Ravi Acharya on the structure and function of the angiotensin converting enzyme and other metalloproteases, with the aim of developing novel inhibitors of therapeutic value.
Christopher Yates completed his undergraduate BSc at the University of Cape Town (UCT), where he specialized in Biochemistry and Microbiology. He pursued his postgraduate studies at the Institute of Infectious Diseases and Molecular Medicine (IDM) at UCT with a focus on Medical Biochemistry, where he started his research on angiotensinconverting enzyme (ACE). Here he investigated the role of chloride in ACE function and catalysis, beginning with his BSc Honours degree and culminating in his PhD being awarded for a thesis that provided a compelling framework for the understanding this important aspect of ACE function. His PhD will go a long way towards furthering our understanding of ACE biochemistry and ultimately towards the design of improved domain-selective inhibitors, critical in the effective and safe treatment of hypertension. Subsequent to his PhD, Christopher has chosen to pursue a career in strategy and innovation consulting and is a senior associate at Ernst & Young.
Edward Sturrock is a full professor of Medical Biochemistry in the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town (UCT). He received his PhD at UCT in 1993 on the synthesis and metabolism of bilirubin under the mentorship of James Bull and Ralph Kirsch. Following his PhD, he went on to do a postdoctoral fellowship at Harvard Medical School where he started his research on angiotensin-converting enzyme (ACE). In 2003 he was awarded a Wellcome Trust International Senior Research Fellowship for his work on ACE. His research interests include: structure-function aspects of metallopeptidases; structure-based design of novel ACE inhibitors; and the molecular machinery involved in the processing of the membrane-anchored proteins. He is a Fellow and vice-president of the Royal Society of South Africa, a Fellow of the University of Cape Town, an honorary professor at the University of Bath, and a council member of the International Proteolysis Society. He has published over 90 papers in peer-reviewed international journals and four patents.
K. Ravi Acharya is a Professor of Structural Molecular Biology at the University of Bath, UK. After a PhD in X-ray crystallography from Bangalore University (India) he was a post-doctoral fellow in the Laboratory of Molecular Biophysics at Oxford (UK). Since relocating to Bath in 1990, he has established a strong structural molecular biology programme and his central scientific interest has been in understanding the ‘structural basis of protein function in human health’ particularly angiogenic molecules and molecules involved in inflammatory processes and functions in the vascular system such as angiotensin-I converting enzyme (ACE).
Acknowledgments
This work was supported by the Medical Research Council (UK) through a project grant (number G1001685) and a Wellcome Trust (UK) equipment grant (number 088464) to K.R.A. This study was also supported by the University of Cape Town and the South African National Research Foundation (E.D.S., C.J.Y.).
References
Abadir, P.M., Walston, J.D., and Carey, R.M. (2012). Subcellular characteristics of functional intracellular renin-angiotensin systems. Peptides 38, 437–445.Search in Google Scholar
Andrade, M.C., Quinto, B.M., Carmona, A.K., Ribas, O.S., Boim, M.A., Schor, N., and Casarini, D.E. (1998). Purification and characterization of angiotensin I-converting enzymes from mesangial cells in culture. J. Hypertens. 16, 2063–2074.Search in Google Scholar
Anthony, K.S., Corradi, H.R., Schwager, S.L., Redelinghuys, P., Georgiadis, D., Dive, V., Acharya, K.R. and Sturrock, E.D. (2010). The N domain of human angiotensin I-converting enzyme: the role of N-glycosylation and the crystal structure in complex with an N domain specific phosphinic inhibitor RXP407. J. Biol. Chem. 285, 35685–35693.Search in Google Scholar
Anthony, C.S., Masuyer, G., Sturrock, E.D., and Acharya, K.R. (2012). Structure Based Drug Design of Angiotensin-I Converting Enzyme Inhibitors. Curr. Med. Chem. 19, 845–855.Search in Google Scholar
Azizi, M., Rousseau, A., Ezan, E., Guyene, T.-T., Michelet, S., Grognet, J-M., Lenfant, M., Corvol, P., and Ménard, J. (1996). Acute angiotensin-converting enzyme inhibition increases the plasma level of the natural stem cell regulator N-acetyl-seryl-aspartyl-lysyl-proline. J. Clin. Invest. 97, 839–844.Search in Google Scholar
Azizi, M., Ezan, E., Nicolet, L., Grognet, J.M., and Menard, J. (1997). High plasma level of N-acetyl-seryl-aspartyl-lysyl-proline: a new marker of chronic angiotensin-converting enzyme inhibition. Hypertension. 30, 1015–1019.Search in Google Scholar
Barnes, K., Matsas, R., Hooper, N.M., Turner, A.J., and Kenny, A.J. (1988). Endopeptidase-24.11 is striosomally ordered in pig brain and, in contrast to aminopeptidase N and peptidyl dipeptidase A (‘angiotensin converting enzyme’), is a marker for a set of striatal efferent fibres. Neuroscience. 27, 799–817.Search in Google Scholar
Baudin, B. (2002). New aspects on angiotensin-converting enzyme: from gene to disease. Clin. Chem. Lab. Med. 40, 256–265.Search in Google Scholar
Beneteau, B., Baudin, B., Morgant, G., Giboudeau, J., and Baumann, F.C. (1986). Automated kinetic assay of angiotensin-converting enzyme in serum. Clin. Chem. 32, 884–886.Search in Google Scholar
Bernstein, K.E., Ong, F.S., Blackwell, W.L., Shah, K.H., Giani, J.F., Gonzalez-Villalobos, R.A., Shen, X.Z., Fuchs, S., Touyz, R.M. (2012). A modern understanding of the traditional and nontraditional biological functions of angiotensin-converting enzyme. Pharmacol. Rev. 65, 1–46.Search in Google Scholar
Bernstein, K.E., Koronyo, Y., Salumbides, B.C., Sheyn, J., Pelissier, L., Lopes, D.H., Shah, K.H., Bernstein, E.A., Fuchs, D.T., Yu, J.J., et al. (2014). Angiotensin-converting enzyme overexpression in myelomonocytes prevents Alzheimer’s-like cognitive decline. J. Clin. Invest. doi: 10.1172/JCI66541.Search in Google Scholar
Bhoola, K.D., Figueroa, C.D., and Worthy, K. (1992). Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol. Rev. 44, 1–80.Search in Google Scholar
Binevski, P.V., Sizova, E.A., Pozdnev, V.F., and Kost, O.A. (2003). Evidence for the negative cooperativity of the two active sites within bovine somatic angiotensin-converting enzyme. FEBS Lett. 550, 84–88.Search in Google Scholar
Bonnet, D., Lemoine, F.M., Pontvert-Delucq, S., Baillou, C., Najman, A., and Guigon, M. (1993). Direct and reversible inhibitory effect of the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (Seraspenide) on the growth of human CD34+ subpopulations in response to growth factors. Blood. 82, 3307–3314.Search in Google Scholar
Chai, S.Y., McKinley, M.J., and Mendelsohn, F.A. (1987). Distribution of angiotensin converting enzyme in sheep hypothalamus and medulla oblongata visualized by in vitro autoradiography. Clin. Exp. Hypertens. A. 9, 449–460.Search in Google Scholar
Chen, Y.N., and Riordan, J.F. (1990). Identification of essential tyrosine and lysine residues in angiotensin converting enzyme: evidence for a single active site. Biochemistry 29, 10493–10498.Search in Google Scholar
Corradi, R., Acharya, R.K., and Sturrock, E.D. (2006). Structure of testis ACE glycosylation mutants and evidence for conserved domain movement. Biochemistry 45, 12654–12663.Search in Google Scholar
Corradi, H.R., Chitapi, I., Sewell, B.T., Georgiadis, D., Dive, V., Sturrock, E.D., and Acharya, K.R. (2007). The structure of testis angiotensin-converting enzyme in complex with the C -domain-specific inhibitor RXPA380. Biochemistry 46, 5473–5478.Search in Google Scholar
Cristovam, P.C., Arnoni, C.P., Andrade, M.C., Casarini, D.E., Pereira, L.G., Schor, N., and Boim, M.A. (2008). Glucose-stimulated human mesangial cells ACE-dependent and chymase-dependent angiotensin II generation in normal and glucose-stimulated human mesangial cells. Exp. Biol. Med. 233, 1035–1043.Search in Google Scholar
Csikós, T., Chung, O., and Unger, T. (1998). Receptors and their classification: focus on angiotensin II and the AT2 receptor. J. Hum. Hypertens. 12, 311–318.Search in Google Scholar
Danilov, S., Balyasnikova, I.V., Albrecht, R.F., and Kost, O.A. (2008). Simultaneous determination of ACE activity with 2 substrates provides information on the status of somatic ACE and allows detection of inhibitors in human blood. J. Cardiovasc. Pharmacol. 52, 90–103.Search in Google Scholar
De Koninck, Y. (2007). Altered chloride homeostasis in neurological disorders: a new target. Curr. Opin. Pharmacol. 7, 93–99.Search in Google Scholar
Deddish, P.A., Wang, J., Michel, B., Morris, P.W., Davidson, N.O., Skidgel, R.A., and Erdös, E.G. (1994). Naturally occurring active N-domain of human angiotensin I-converting enzyme. Proc. Natl. Acad. Sci. USA 91, 7807–7811.Search in Google Scholar
Defendini, R., Zimmerman, E.A., Weare, J.A., Alhenc-Gelas, F., and Erdös, E.G. (1983). Angiotensin-converting enzyme in epithelial and neuroepithelial cells. Neuroendocrinology 37, 32–40.Search in Google Scholar
Douglas, R.G., Sharma, R.K., Masuyer, G., Lubbe, L., Zamora, I., Acharya, K.R., Chibale, K., and Sturrock, E.D. (2014). Fragment-based design for the development of N-domain-selective angiotensin-1-converting enzyme inhibitors. Clin. Sci. (Lond.) 126, 305–313.Search in Google Scholar
Dutzler, R., Campbell, E.B., Cadene, M., Chait, B.T., and MacKinnon, R. (2002). X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity. Nature 415, 287–294.Search in Google Scholar
Ehlers, M.R. and Riordan, J.F. (1989). Angiotensin-converting enzyme: new concepts concerning its biological role. Biochemistry 28, 5311–5318.Search in Google Scholar
Ehlers, M.R., Chen, Y.N., and 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.Search in Google Scholar
Ehlers, M.R., Chen, Y.N., and Riordan, J.F. (1992). The unique N-terminal sequence of testis angiotensin-converting enzyme is heavily O-glycosylated and unessential for activity or stability. Biochem. Biophys. Res. Commun. 183, 199–205.Search in Google Scholar
Ehlers, M.R., Schwager, S.L., Scholle, R.R., Manji, G.A., Brandt, W.F., and Riordan, J.F. (1996). Proteolytic release of membrane-bound angiotensin-converting enzyme: role of the juxtamembrane stalk sequence. Biochemistry 35, 9549–9559.Search in Google Scholar
Elkins, J.S., Douglas, V.C., and Johnston, S.C. (2004). Alzheimer disease risk and genetic variation in ACE: a meta-analysis. Neurology. 62, 363–368.Search in Google Scholar
Erdos, E.G. and Yang, H.Y. (1967). An enzyme in microsomal fraction of kidney that inactivates bradykinin. Life Sci. 6, 569–574.Search in Google Scholar
Eriksson, U., Danilczyk, U., and Penninger, J.M. (2002). Just the beginning: novel functions for angiotensin-converting enzymes. Curr. Biol. 12, R745–R752.Search in Google Scholar
Esther, C.R., Howard, T.E., Marino, E.M., Goddard, J.M., Capecchi, M.R., and Bernstein, K.E. (1996). Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility. Lab. Invest. 74, 953–965.Search in Google Scholar
Fernandez, M., Liu, X., Wouters, M.A., Heyberger, S., and Husain, A. (2001). Angiotensin I-converting enzyme transition state stabilization by HIS1089: evidence for a catalytic mechanism distinct from other gluzincin metalloproteinases. J. Biol. Chem. 276, 4998–5004.Search in Google Scholar
Fuchs, S., Xiao, H.D., Cole, J.M., Adams, J.W., Frenzel, K., Michaud, A., Zhao, H., Keshelava, G., Capecchi, M.R., Corvol, P., and Bernstein, K.E. (2004). Role of the N-terminal catalytic domain of angiotensin-converting enzyme investigated by targeted inactivation in mice. J. Biol. Chem. 279, 15946–15953.Search in Google Scholar
Fuchs, S., Frenzel, K., Hubert, C., Lyng, R., Muller, L., Michaud, A., Xiao, H.D., Adams, J.W., Capecchi, M.R., Corvol, P., et al. (2005). Male fertility is dependent on dipeptidase activity of testis ACE. Nat. Med. 11, 1140–1142.Search in Google Scholar
Fuchs, S., Xiao, H.D., Hubert, C., Michaud, A., Campbell, D.J., Adams, J.W., Capecchi, M.R., Corvol, P., and Bernstein, K.E. (2008). Angiotensin-converting enzyme C-terminal catalytic domain is the main site of angiotensin I cleavage in vivo. Hypertension 51, 267–274.Search in Google Scholar
Gasparo, M., Husain, A., Alexander, W., Catt, K.J., Chiu, A.T., Drew, M., Goodfriend, T., Harding, J.W., Inagami, T., and Timmermans, P.B. (1995). Proposed update of angiotensin receptor nomenclature. Hypertension 25, 924–927.Search in Google Scholar
Goldblatt, H., Lynch, J., Hanzal, R.F., and Summerville, W.N. (1934). Studies on experimental hypertension.I. The production of persistent elevation of systolic blood pressure by means of renal ischemia. J. Exp. Med. 59, 347–379.Search in Google Scholar
Gonzalez-Villalobos, R.A., Shen, X.Z., Bernstein, E.A., Janjulia, T., Taylor, B., Giani, J.F., Blackwell, W.L., Shah, K.H., Shi, P.D., Fuchs, S., et al. (2013). Rediscovering ACE: novel insights into the many roles of the angiotensin-converting enzyme. J. Mol. Med. (Berl.) 91, 1143–1154.Search in Google Scholar
Guimarães, P.B., Alvarenga, É.C., Siqueira, P.D., Paredes-Gamero, E.J., Sabatini, R.A., Morais, R.L., Reis, R.I., Santos, E.L., Teixeira, L.G., Casarini, D.E., et al. (2011). Angiotensin II binding to angiotensin I-converting enzyme triggers calcium signaling. Hypertension. 57, 965–972.Search in Google Scholar
Guy, J.L., Jackson, R.M., Acharya, K.R., Sturrock, E.D., Hooper, N.M., and Turner, A.J. (2003). Angiotensin-converting enzyme-2 (ACE2): comparative modeling of the active site, specificity requirements, and chloride dependence. Biochemistry 42, 13185–13192.Search in Google Scholar
Hagaman, J.R., Moyer, J.S., Bachman, E.S., Sibony, M., Magyar, P.L., Welch, J.E., Smithies, O., Krege, J.H., and O’Brien, D.A. (1998). Angiotensin-converting enzyme and male fertility. Proc. Natl. Acad. Sci. USA 95, 2552–2557.Search in Google Scholar
Hanesworth, J.M., Sardinia, M.F., Krebs, L.T., Hall, K.L., and Harding, J.W. (1993). Elucidation of a specific binding site for angiotensin II(3–8), angiotensin IV, in mammalian heart membranes. J. Pharmacol. Exp. Ther. 266, 1036–1042.Search in Google Scholar
Hemming, M.L. and Selkoe, D.J. (2005). Amyloid β-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor. J. Biol. Chem. 280, 37644–37650.Search in Google Scholar
Hille, B. (1992). Ionic channels of excitable membranes (Sunderland, MA, Sinauer Associates).Search in Google Scholar
Ho, B.K., and Gruswitz, F. (2008). HOLLOW: Generating accurate representations of channel and interior surfaces in molecular structures. BMC Struct. Biol. 8, 49.Search in Google Scholar
Holmquist, B., Bünning, P., and Riordan, J.F. (1979). A continuous spectrophotometric assay for angiotensin converting enzyme. Anal. Biochem. 95, 540–548.Search in Google Scholar
Horiuchi, M. (1996). Functional aspects of angiotensin type 2 receptor. Adv. Exp. Med. Biol. 396, 217–224.Search in Google Scholar
Houssay, B.A. and Fasciolo, J.C. (1937). Secretion hipertensora del rinon isquemaido. Rev. Soc. Argent. Biol. 13, 284–294.Search in Google Scholar
Howard, T.E., Shai, S.Y., Langford, K.G., Martin, B.M., and Bernstein, K.E. (1990). Transcription of testicular angiotensin-converting enzyme (ACE) is initiated within the 12th intron of the somatic ACE gene. Mol. Cell Biol. 10, 4294–4302.Search in Google Scholar
Hubert, C., Houot, A.M., Corvol, P., and Soubrier, F. (1991). Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene. J. Biol.Chem. 266, 15377–15383.Search in Google Scholar
Inagami, T. (1994). The renin-angiotensin system. Essays Biochem. 28, 147–164.Search in Google Scholar
Inoue, H., Mori, S., Morishima, S., and Okada, Y. (2005). Volume-sensitive chloride channels in mouse cortical neurons: characterization and role in volume regulation. Eur. J. Neurosci. 21, 1648–1658.Search in Google Scholar
Jaspard, E., Wei, L., and Alhenc-Gelas, F. (1993). Differences in the properties and enzymatic specificities of the two active sites of angiotensin I-converting enzyme (kininase II). Studies with bradykinin and other natural peptides. J. Biol. Chem. 268, 9496–9503.Search in Google Scholar
Jenkins, T.A., Mendelsohn, F.A., and Chai, S.Y. (1997). Angiotensin-converting enzyme modulates dopamine turnover in the striatum. J. Neurochem. 68, 1304–1311.Search in Google Scholar
Jeyendran, R.S., Van der Ven, H.H., Rosecrans, R., Perez-Pelaez, M., Al-Hasani, S., and Zaneveld, L.J.D. (1989). Chemical constituents of human seminal plasma: relationship to fertility. Andrologia 21, 423–428.Search in Google Scholar
Junot, C., Gonzales, M.F., Ezan, E., Cotton, J., Vazeux, G., Michaud, A., Azizi, M., Vassiliou, S., Yiotakis, A., Corvol, P., et al. (2001). RXP 407, a selective inhibitor of the N-domain of angiotensin I-converting enzyme, blocks in vivo the degradation of hemoregulatory peptide acetyl-Ser-Asp-Lys-Pro with no effect on angiotensin I hydrolysis. J. Pharmacol. Exp. Ther. 297, 606–611.Search in Google Scholar
Kehoe, P.G., Russ, C., McIlory, S., Williams, H., Holmans, P., Holmes, C., Liolitsa, D., Vahidassr, D., Powell, J., McGleenon, B. et al. (1999). Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease. Nat. Genet. 21, 71–72.Search in Google Scholar
Krege, J.H., John, S.W., Langenbach, L.L., Hodgin, J.B., Hagaman, J.R., Bachman, E.S., Jennette, J.C., O’Brien, D.A., and Smithies, O. (1995). Male-female differences in fertility and blood pressure in ACE-deficient mice. Nature 375, 146–148.Search in Google Scholar
Kroger, W.L., Douglas, R.G., O’Neill, H.G., Dive, V. and Sturrock, E.D. (2009). Investigating the domain specificity of phosphinic inhibitors RXPA380 and RXP407 in angiotensin-converting enzyme. Biochemistry 48, 8405–8412.Search in Google Scholar
Kroeger, D., Tamburri, A., Amzica, F., and Sík, A. (2010). Activity-dependent layer-specific changes in the extracellular chloride concentration and chloride driving force in the rat hippocampus. J. Neurophysiol. 103, 1905–1914.Search in Google Scholar
Lazard, D., Briend-Sutren, M.M., Villageois, P., Mattei, M.G., Strosberg, A.D., and Nahmias, C. (1994). Molecular characterization and chromosome localization of a human angiotensin I AT2 receptor gene highly expressed in fetal tissues. Receptors Channels 2, 271–280.Search in Google Scholar
Lehmann, D.J., Cortina-Borja, M., Warden, D.R., Smith, A.D., Sleegers, K., Prince, J.A., van Duijn, C.M., and Kehoe, P.G. (2005). Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer’s disease. Am. J. Epidemiol. 162, 305–317.Search in Google Scholar
Lenfant, M., Wdzieczak-Bakala, J., Guittet, E., Prome, J.C., Sotty, D., and Frindel, E. (1989). Inhibitor of hematopoietic pluripotent stem cell proliferation: purification and determination of its structure. Proc. Natl. Acad. Sci. USA 86, 779–782.Search in Google Scholar
Liu, X., Fernandez, M., Wouters, M.A., Heyberger, S., and Husain, A. (2001). Arg(1098) is critical for the chloride dependence of human angiotensin I-converting enzyme C-domain catalytic activity. J. Biol. Chem. 276, 33518–33525.Search in Google Scholar
Lodish, H.F. (1999). Molecular Cell Biology (NY, USA: Freeman, W.H).Search in Google Scholar
Masuyer, G., Schwager, S.L., Sturrock, E.D., Isaac, R.E., and Acharya, K.R. (2012). Molecular recognition and regulation of human angiotensin-I converting enzyme (ACE) activity by natural inhibitory peptides Sci. Rep. 2, 717.Search in Google Scholar
Matsas, R., Kenny, A.J., and Turner, A.J. (1984). The metabolism of neuropeptides. The hydrolysis of peptides, including enkephalins, tachykinins and their analogues, by endopeptidase-24.11. Biochem. J. 223, 433–440.Search in Google Scholar
Matthews, B.W. (1988). Structural basis of the action of thermolysin and related zinc peptidases. Acc. Chem. Res. 21, 333–340.Search in Google Scholar
McKinley, M.J., Albiston, A.L., Allen, A.M., Mathai, M.L., May, C.N., McAllen, R.M, Oldfield, B.J., Mendelsohn, F.A., and Chai, S.Y. (2003). The brain renin-angiotensin system: location and physiological roles. Int. J. Biochem. Cell Biol. 35, 901–918.Search in Google Scholar
Michaud, A., Williams T.A., Chauvet, M.T., and Corvol, P. (1997). Substrate dependence of angiotensin I-converting enzyme inhibition: captopril displays a partial selectivity for inhibition of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline hydrolysis compared with that of angiotensin. Mol. Pharmacol. 51, 1070–1076.Search in Google Scholar
Moiseeva, N.A., Binevski, P.V., Baskin, I.I., Palyulin, V.A. and Kost, O.A. (2005). Role of two chloride-binding sites in functioning of testicular angiotensin-converting enzyme. Biochemistry (Mosc.) 70, 1167–1172.Search in Google Scholar
Natesh, R., Schwager, S.L.U., Sturrock, E.D., and Acharya, K.R. (2003). Crystal structure of the human angiotensin-converting enzyme-lisinopril complex. Nature 421, 551–554.Search in Google Scholar
Natesh, R., Schwager, S.L., Evans, H.R., Sturrock, E.D., and Acharya, K.R. (2004). Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme. Biochemistry 43, 8718–8724.Search in Google Scholar
O’Neill, H.G., Redelinghuys, P., Schwager, S.L., and Sturrock, E.D. (2008). The role of glycosylation and domain interactions in the thermal stability of human angiotensin-converting enzyme. Biol. Chem. 389, 1153–1161.Search in Google Scholar
Oba, R., Igarashi, A., Kamata, M., Nagata, K., Takano, S., and Nakagawa, H. (2005). The N-terminal active centre of human angiotensin-converting enzyme degrades Alzheimer amyloid β-peptide. Eur. J. Neurosci. 21, 733–740.Search in Google Scholar
Oblin, A., Danse, M.J., and Zivkovic, B. (1988). Degradation of substance P by membrane peptidases in the rat substantia nigra: effect of selective inhibitors. Neurosci. Lett. 84, 91–96.Search in Google Scholar
Okwan-Duodu, D., Datta, V., Shen, X.Z., Goodridge, H.S., Bernstein, E.A., Fuchs, S., Liu, G.Y., and Bernstein, K.E. (2010). Angiotensin-converting enzyme overexpression in mouse myelomonocytic cells augments resistance to Listeria and methicillin-resistant Staphylococcus aureus. J. Biol. Chem. 285, 39051–39060.Search in Google Scholar
Page, I.H. and Helmer, O.M. (1940). A crystalline pressor substance (angiotonin) resulting from the interaction between renin and renin activator. J. Exp. Med. 71, 29.Search in Google Scholar
Peng, H., Carretero, O.A., Peterson, E.L., and Rhaleb, N-E. (2010). Ac-SDKP inhibits transforming growth factor-β 1-induced differentiation of human cardiac fibroblasts into myofibroblasts. Am. J. Physiol. Heart. Circ. Physiol. 298, H1357–H1364.Search in Google Scholar
Rasoul, S., Carretero, O.A., Peng, H., Cavasin, M.A., Zhuo, J., Sanchez-Mendoza, A., Brigstock, D.R., and Rhaleb, N.E. (2004). Antifibrotic effect of Ac-SDKP and angiotensin-converting enzyme inhibition in hypertension. J. Hypertens. 22, 593–603.Search in Google Scholar
Regoli, D., Rhaleb, N.E., Drapeau, G., Dion, S., Tousignant, C., D’Orléans-Juste, P., and Devillier, P. (1989). Basic pharmacology of kinins: pharmacologic receptors and other mechanisms. Adv. Exp. Med. Biol. 247A, 399–407.Search in Google Scholar
Rice, G.I., Thomas, D.A., Grant, P.J., Turner, A.J., and Hooper, N.M. (2004). Evaluation of angiotensin converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem. J. 383, 45–51.Search in Google Scholar
Rigat, B., Hubert, C., Alhenc-Gelas, F., Cambien, F., Corvol, P., and Soubrier, F. (1990). An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J. Clin. Invest. 86, 1343–1346.Search in Google Scholar
Rosecrans, R.R., Jeyendran, R.S., Perez-Pelaez, M., and Kennedy W.P. (1987). Comparison of biochemical parameters of human blood serum and seminal plasma. Andrologia 19, 625–628.Search in Google Scholar
Rousseau, A., Michaud, A., Chauvet, M.T., and Corvol, P. (1995). The hemoregulatory peptide N-acetyl-Ser-Asp-Lys-Pro is a natural and specific substrate of the N-terminal active site of human angiotensin-converting enzyme. J. Biol. Chem. 270, 3656–3661.Search in Google Scholar
Rousseau-Plasse, A., Lenfant, M., and Potier, P. (1996). Catabolism of the hemoregulatory peptide N-Acetyl-Ser-Asp-Lys-Pro: a new insight into the physiological role of the angiotensin-I-converting enzyme N-active site. Bioorg. Med. Chem.4, 1113–1119.Search in Google Scholar
Rushworth, C.A., Guy, J.L., and Turner, A.J. (2008). Residues affecting the chloride regulation and substrate selectivity of the angiotensin-converting enzymes (ACE and ACE2) identified by site-directed mutagenesis. FEBS J. 275, 6033–6042.Search in Google Scholar
Sadhukhan, R. and Sen, I. (1996). Different glycosylation requirements for the synthesis of enzymatically active angiotensin-converting enzyme in mammalian cells and yeast. J. Biol. Chem. 271, 6429–6434.Search in Google Scholar
Sasaguri, M., Ideishi, M., Ogata, S., Miura, S., Ikeda, M., and Arakawa, K. (1995). Human urinary kallikrein can generate angiotensin II from homologous renin substrates. Hypertens. Res. 18, 33–37.Search in Google Scholar
Savaskan, E. (2005). The role of the brain renin-angiotensin system in neurodegenerative disorders. Curr. Alzheimer Res. 2, 29–35.Search in Google Scholar
Sealey, J.E., Atlas, S.A., Laragh, J.H., Silverberg, M., and Kaplan, A.P. (1979). Initiation of plasma prorenin activation by Hageman factor-dependent conversion of plasma prekallikrein to kallikrein. Proc. Natl. Acad. Sci. USA 76, 5914–5918.Search in Google Scholar
Sen, I., Kasturi, S., Abdul Jabbar, M., and Sen, G.C. (1993). Mutations in two specific residues of testicular angiotensin-converting enzyme change its catalytic properties. J. Biol. Chem. 268, 25748–25754.Search in Google Scholar
Shanmugam, S. and Sandberg, K. (1996). Ontogeny of angiotensin II receptors. Cell Biol. Int. 20, 169–176.Search in Google Scholar
Shapiro, R. and Riordan J.F. (1984). Inhibition of angiotensin converting enzyme: mechanism and substrate dependence. Biochemistry 23, 5225–5233.Search in Google Scholar
Shapiro, R., Holmquist, B., and Riordan, J.F. (1983). Anion activation of angiotensin converting enzyme: dependence on nature of substrate. Biochemistry 22, 3850–3857.Search in Google Scholar
Shen, X.Z., Li, P., Weiss, D., Fuchs, S., Xiao, H.D., Adams, J.A., Williams, I.R., Capecchi, M.R., Taylor, W.R., and Bernstein, K.E. (2007). Mice with enhanced macrophage angiotensin-converting enzyme are resistant to melanoma. Am. J. Pathol. 170, 2122–2134.Search in Google Scholar
Shen, X.Z., Lukacher, A.E., Billet, S., Williams, I.R., and Bernstein, K.E. (2008). Expression of angiotensin-converting enzyme changes major histocompatibility complex class I peptide presentation by modifying C-termini of peptide precursors. J. Biol. Chem. 283, 9957–9965.Search in Google Scholar
Shen, X.Z., Billet, S., Lin, C., Okwan-Duodu, D., Chen, X., Lukacher, A.E., and Bernstein, K.E. (2011). The carboxypeptidase ACE shapes the MHC class I peptide repertoire. Nat. Immunol. 12, 1078–1085.Search in Google Scholar
Sibony, M., Gasc, J.M., Soubrier, F., Alhenc-Gelas, F., and Corvol, P. (1993). Gene expression and tissue localization of the two isoforms of angiotensin I converting enzyme. Hypertension 21, 827–835.Search in Google Scholar
Skeggs, L.T., Marsh, W.H., Kahn, J.R., and Shumway, N.P. (1954). The purification of hypertensin I. J. Exp. Med. 100, 363–370.Search in Google Scholar
Skeggs, L.T., Kahn, J.R., and Shumway, N.P. (1956). The preparation and function of the hypertensin-converting enzyme. J. Exp. Med. 103, 295–299.Search in Google Scholar
Skidgel,R.A. and Erdös, E.G. (1985). Novel activity of human angiotensin I converting enzyme: release of the NH2- and COOH-terminal tripeptides from the luteinizing hormone-releasing hormone. Proc. Natl. Acad. Sci. USA 82, 1025–1029.Search in Google Scholar
Skidgel, R.A. and Erdös, E.G. (2004). Angiotensin converting enzyme (ACE) and neprilysin hydrolyze neuropeptides: a brief history, the beginning and follow-ups to early studies. Peptides 25, 521–525.Search in Google Scholar
Skidgel, R.A., Defendini, R., and Erdos, E.G. (1987). In: Neuropeptides and their Neuropeptidases. A.J. Turner, ed. (Chichester, UK: V.C.H. Ellis- Horwood), pp. 165–182.Search in Google Scholar
Soubrier, F., Alhenc-Gelas, F., Hubert, C., Allegrini, J., John, M., Tregear, G., and Corvol, P. (1988). Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning. Proc. Natl. Acad. Sci. USA 85, 9386–9390.Search in Google Scholar
Strittmatter, S.M., Lo, M.M., Javitch, J.A., and Snyder, S.H. (1984). Autoradiographic visualization of angiotensin-converting enzyme in rat brain with [3H]captopril: localization to a striatonigral pathway. Proc. Natl. Acad. Sci. USA 81, 1599–1603.Search in Google Scholar
Sturrock, E.D., Natesh, R., van Rooyen, J.M., and Acharya, K.R. (2004). Structure of angiotensin I-converting enzyme. Cell. Mol. Life Sci. 61, 2677–2686.Search in Google Scholar
Takada, Y., Hiwada, K., Akutsu, H., Hashimoto, A., and Kokubu, T. (1984). The immunocytochemical detection of angiotensin-converting enzyme in alveolar macrophages from patients with sarcoidosis. Lung 162, 317–323.Search in Google Scholar
Timmermans, P.B., Benfield, P., Chiu, A.T., Herblin, W.F., Wong, P.C., and Smith, R.D. (1992). Angiotensin II receptors and functional correlates. Am. J. Hypertens. 5, 221S–235S.Search in Google Scholar
Timmermans, P.B., Wong, P.C., Chiu, A.T., Herblin, W.F., Benfield, P., Carini, D.J., Lee, R.J., Wexler, R.R., Saye, J.A., and Smith, R.D. (1993). Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol. Rev. 45, 205–251.Search in Google Scholar
Turner, A.J. and Hooper, N.M. (2002). The angiotensin-converting enzyme gene family: genomics and pharmacology. Trends Pharmacol. Sci. 23, 177–183.Search in Google Scholar
Tzakos, A.G., Galanis, A.S., Spyroulias, G.A., Cordopatis, P., Manessi-Zoupa, E., and Gerothanassis, I.P. (2003). Structure-function discrimination of the N- and C- catalytic domains of human angiotensin-converting enzyme: implications for Cl- activation and peptide hydrolysis mechanisms. Protein Eng. 16, 993–1003.Search in Google Scholar
van den Buuse, M., Zheng, T.W., Walker, L.L., and Denton, D.A. (2005). Angiotensin-converting enzyme (ACE) interacts with dopaminergic mechanisms in the brain to modulate prepulse inhibition in mice. Neurosci. Lett. 380, 6–11.Search in Google Scholar
Voronov, S., Zueva, N., Orlov, V., Arutyunyan, A., and Kost, O. (2002). Temperature-induced selective death of the C-domain within angiotensin-converting enzyme molecule. FEBS Lett. 522, 77–82.Search in Google Scholar
Wang, D., Carretero, O.A., Yang, X.Y., Rhaleb, N.-E., Liu, Y.-H., Liao, T.-D., and Yang, X.-P. (2004). N-acetyl-seryl-aspartyl-lysyl-proline stimulates angiogenesis in vitro and in vivo. Am. J. Physiol. Heart. Circ. Physiol. 287, H2099–H2105.Search in Google Scholar
Watermeyer, J.M., Sewell, B.T., Schwager, S.L., Natesh, R., Corradi, H.R., Acharya, K.R., and Strurrock, E.D. (2006). Structure of testis ACE glycosylation mutants and evidence for conserved domain movement. Biochemistry 45, 12654–12663.Search in Google Scholar
Wei, L., Alhenc-Gelas, F., Corvol, P., and Clauser, E. (1991a). The two homologous domains of human angiotensin I-converting enzyme are both catalytically active. J. Biol. Chem. 266, 9002–9008.Search in Google Scholar
Wei, L., Alhenc-Gelas, F., Soubrier, F., Michaud, A., Corvol, P., and Clauser, E. (1991b). Expression and characterization of recombinant human angiotensin I-converting enzyme. Evidence for a C-terminal transmembrane anchor and for a proteolytic processing of the secreted recombinant and plasma enzymes. J. Biol. Chem. 266, 5540–5546.Search in Google Scholar
Wei, L., Clauser, E., Alhenc-Gelas, F., and Corvol, P. (1992). The two homologous domains of human angiotensin I-converting enzyme interact differently with competitive inhibitors. J. Biol. Chem. 267, 13398–13405.Search in Google Scholar
Woodman, Z.L., Oppong, S.Y., Cook, S., Hooper, N.M., Schwager, S.L.U., Brandt, W.F., Ehlers, M.R.W., and Sturrock, E.D. (2000). Shedding of somatic angiotensin-converting enzyme (ACE) is inefficient compared with testis ACE despite cleavage at identical stalk sites. Biochemical J. 347, 711–718.Search in Google Scholar
Wright, J.W. and Harding, J.W. (2004). The brain angiotensin system and extracellular matrix molecules in neural plasticity, learning, and memory. Progr. Neurobiol. 72, 263–293.Search in Google Scholar
Yamaguchi, T., Carretero, O.A., and Scicli, A.G. (1991). A novel serine protease with vasoconstrictor activity coded by the kallikrein gene S3. J. Biol. Chem. 266, 5011–5017.Search in Google Scholar
Yang, H.Y., Erdös, E.G., and Levin, Y. (1970). A dipeptidyl carboxypeptidase that converts angiotensin I and inactivates bradykinin. Biochim. Biophys. Acta 214, 374–376.Search in Google Scholar
Yang, H.Y., Erdös, E.G., and Levin, Y. (1971). Characterization of a dipeptide hydrolase (kininase II: angiotensin I converting enzyme). J. Pharmacol. Exp. Ther. 177, 291–300.Search in Google Scholar
Yates, C.J., Masuyer, G., Schwager, S.L., Akif, M., Sturrock, E.D., and Acharya, K.R. (2014). Molecular and thermodynamic mechanisms of the chloride-dependent human angiotensin-I-converting enzyme (ACE). J. Biol Chem. 289, 1798–1814.Search in Google Scholar
Yu, X.C., Sturrock, E.D., Wu, Z.C., Biemann, K., Ehlers, M.R.W., and Riordan, J.F. (1997). Identification of N-linked glycosylation sites in human testis angiotensin-converting enzyme and expression of an active deglycosylated forms. J. Biol. Chem. 272, 3511–3519.Search in Google Scholar
Zou, K., Yamaguchi, H., Akatsu, H., Sakamoto, T., Ko, M., Mizoguchi, K., Gong, J.S., Yu, W., Yamamoto, T., Kosaka, K., et al. (2007). Angiotensin-converting enzyme converts amyloid beta-protein 1–42 (Aβ(1–42)) to Aβ(1–40), and its inhibition enhances brain Aβ deposition. J. Neurosci. 27, 8628–8635.Search in Google Scholar
©2014 by De Gruyter
