Advances in Structural Biology of ACE and Development of Domain Selective ACE-inhibitors

Author(s): Mája Polakovičová*, Josef Jampílek

Journal Name: Medicinal Chemistry

Volume 15 , Issue 6 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: The Angiotensin-I converting enzyme (ACE) is one of the most important components of the renin-angiotensin-aldosterone system controlling blood pressure and renal functions. Inhibitors of ACE are first line therapeutics used in the treatment of hypertension and related cardiovascular diseases. Somatic ACE consists of two homologous catalytic domains, the C- and N-domains. Recent findings have shown that although both domains are highly homologous in structure, they may have different physiological functions. The C-domain is primarily involved in the control of blood pressure, in contrast to the N-domain that is engaged in the regulation of hematopoietic stem cell proliferation. The currently available ACE inhibitors have some adverse effects that can be attributed to the non-selective inhibition of both domains. In addition, specific Ndomain inhibitors have emerged as potential antifibrotic drugs. Therefore, ACE is still an important drug target for the development of novel domain-selective drugs not only for the cardiovascular system but also for other systems.

Objective: Detailed structural information about interactions in the protein-ligand complex is crucial for rational drug design. This review highlights the structural information available from crystallographic data which is essential for the development of domain selective inhibitors of ACE.

Methods: Over eighty crystal complexes of ACE are placed into the Protein Database. An overview of X-ray ACE complexes with various inhibitors in C- and N-domains and an analysis of their binding mode have given mechanistic explanation of the structural determinants of selective ligand binding. In addition, ACE domain selective inhibitors with dual modes of action in complexes with ACE are also discussed.

Conclusion: Selectivity of ACE inhibitors for the N- and C-domain is controlled by subtle differences in the amino-acids forming the active site. Reported studies of crystal complexes of inhibitors in the C- and N-domains revealed that most selective inhibitors interact with non-conserved amino-acids between domains and have distinct interactions with the residues in the S2 and S2’ subsites of the ACE catalytic site. Moreover, unusual binding of the second molecule of inhibitors in the binding cavity opens new possibilities of exploiting more distant regions of the catalytic center in structure-based design of novel drugs.

Keywords: Angiotensin converting enzyme (ACE), C-domain, N-domain, selective inhibitor, crystal structure, non-prime binding.

[1]
Epstein, B.J.; Leonard, P.T.; Shah, N.K. The evolving landscape of RAAS inhibition: From ACE inhibitors to ARBs, to DRIs and beyond. Expert Rev. Cardiovasc. Ther., 2012, 10(6), 713-725.
[http://dx.doi.org/10.1586/erc.12.63] [PMID: 22894628]
[2]
Hanif, K.; Bid, H.K.; Konwar, R. Reinventing the ACE inhibitors: Some old and new implications of ACE inhibition. Hypertens. Res., 2010, 33(1), 11-21.
[http://dx.doi.org/10.1038/hr.2009.184] [PMID: 19911001]
[3]
Bicket, D.P. Using ACE inhibitors appropriately. Am. Fam. Physician, 2002, 66(3), 461-468.
[PMID: 12182524]
[4]
Morimoto, T.; Gandhi, T.K.; Fiskio, J.M.; Seger, A.C.; So, J.W.; Cook, E.F.; Fukui, T.; Bates, D.W. An evaluation of risk factors for adverse drug events associated with angiotensin-converting enzyme inhibitors. J. Eval. Clin. Pract., 2004, 10(4), 499-509.
[http://dx.doi.org/10.1111/j.1365-2753.2003.00484.x] [PMID: 15482412]
[5]
Adam, A.; Cugno, M.; Molinaro, G.; Perez, M.; Lepage, Y.; Agostoni, A. Aminopeptidase P in individuals with a history of angio-oedema on ACE inhibitors. Lancet, 2002, 359(9323), 2088-2089.
[http://dx.doi.org/10.1016/S0140-6736(02)08914-6] [PMID: 12086766]
[6]
Yeo, W.W.; Chadwick, I.G.; Kraskiewicz, M.; Jackson, P.R.; Ramsay, L.E. Resolution of ACE inhibitor cough: Changes in subjective cough and responses to inhaled capsaicin, intradermal bradykinin and Substance-P. Br. J. Clin. Pharmacol., 1995, 40(5), 423-429.
[PMID: 8703645]
[7]
Soubrier, F.; Alhenc-Gelas, F.; Hubert, C.; Allegrini, J.; John, M.; Tregear, G.; Corvol, P. Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning. Proc. Natl. Acad. Sci. USA, 1988, 85(24), 9386-9390.
[http://dx.doi.org/10.1073/pnas.85.24.9386] [PMID: 2849100]
[8]
Turner, A.J.; Hooper, N.M. The angiotensin-converting enzyme gene family: Genomics and pharmacology. Trends Pharmacol. Sci., 2002, 23(4), 177-183.
[http://dx.doi.org/10.1016/S0165-6147(00)01994-5] [PMID: 11931993]
[9]
Hubert, C.; Houot, A.M.; Corvol, P.; Soubrier, F. Structure of the Angiotensin I-Converting Enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene. J. Biol. Chem., 1991, 266(23), 15377-15383.
[PMID: 1651327]
[10]
Bernstein, K.E.; Shen, X.Z.; Gonzalez-Villalobos, R.A.; Billet, S.; Okwan-Duodu, D.; Ong, F.S.; Fuchs, S. Different in vivo functions of the two catalytic domains of angiotensin-converting enzyme (ACE). Curr. Opin. Pharmacol., 2011, 11(2), 105-111.
[http://dx.doi.org/10.1016/j.coph.2010.11.001] [PMID: 21130035]
[11]
van Esch, J.H.; Tom, B.; Dive, V.; Batenburg, W.W.; Georgiadis, D.; Yiotakis, A.; van Gool, J.M.; de Bruijn, R.J.; de Vries, R.; Danser, A.H. Selective angiotensin-converting enzyme C-domain inhibition is sufficient to prevent angiotensin I-induced vasoconstriction. Hypertension, 2005, 45(1), 120-125.
[http://dx.doi.org/10.1161/01.HYP.0000151323.93372.f5] [PMID: 15583077]
[12]
Wei, L.; Clauser, E.; Alhenc-Gelas, F.; Corvol, P. The two homologous domains of human angiotensin I-converting enzyme interact differently with competitive inhibitors. J. Biol. Chem., 1992, 267(19), 13398-13405.
[PMID: 1320019]
[13]
Georgiadis, D.; Beau, F.; Czarny, B.; Cotton, J.; Yiotakis, A.; Dive, V. Roles of the two active sites of somatic angiotensin-converting enzyme in the cleavage of angiotensin I and bradykinin: Insights from selective inhibitors. Circ. Res., 2003, 93(2), 148-154.
[http://dx.doi.org/10.1161/01.RES.0000081593.33848.FC] [PMID: 12805239]
[14]
Fernandez, J.H.; Hayashi, M.A.; Camargo, A.C.; Neshich, G. Structural basis of the lisinopril-binding specificity in N- and C-domains of human somatic ACE. Biochem. Biophys. Res. Commun., 2003, 308(2), 219-226.
[http://dx.doi.org/10.1016/S0006-291X(03)01363-9] [PMID: 12901857]
[15]
Rousseau, A.; Michaud, A.; Chauvet, M.T.; Lenfant, M.; Corvol, P. 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., 1995, 270(8), 3656-3661.
[http://dx.doi.org/10.1074/jbc.270.8.3656] [PMID: 7876104]
[16]
Wei, L.; Alhenc-Gelas, F.; Corvol, P.; Clauser, E. The two homologous domains of human angiotensin I-converting enzyme are both catalytically active. J. Biol. Chem., 1991, 266(14), 9002-9008.
[PMID: 1851160]
[17]
Sharma, R.K.; Douglas, R.G.; Louw, S.; Chibale, K.; Sturrock, E.D. New ketomethylene inhibitor analogues: Synthesis and assessment of structural determinants for N-domain selective inhibition of angiotensin-converting enzyme. Biol. Chem., 2012, 393(6), 485-493.
[http://dx.doi.org/10.1515/hsz-2012-0127] [PMID: 22628311]
[18]
Deddish, P.A.; Marcic, B.; Jackman, H.L.; Wang, H.Z.; Skidgel, R.A.; Erdös, E.G. N-domain-specific substrate and C-domain inhibitors of angiotensin-converting enzyme: Angiotensin-(1-7) and keto-ACE. Hypertension, 1998, 31(4), 912-917.
[http://dx.doi.org/10.1161/01.HYP.31.4.912] [PMID: 9535414]
[19]
Oba, R.; Igarashi, A.; Kamata, M.; Nagata, K.; Takano, S.; Nakagawa, H. The N-terminal active centre of human angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide. Eur. J. Neurosci., 2005, 21(3), 733-740.
[http://dx.doi.org/10.1111/j.1460-9568.2005.03912.x] [PMID: 15733091]
[20]
Larmuth, K.M.; Masuyer, G.; Douglas, R.G.; Schwager, S.L.; Acharya, K.R.; Sturrock, E.D. Kinetic and structural characterization of amyloid-β peptide hydrolysis by human angiotensin-1-converting enzyme. FEBS J., 2016, 283(6), 1060-1076.
[http://dx.doi.org/10.1111/febs.13647] [PMID: 26748546]
[21]
Sharma, U.; Rhaleb, N.E.; Pokharel, S.; Harding, P.; Rasoul, S.; Peng, H.; Carretero, O.A. Novel anti-inflammatory mechanisms of N-Acetyl-Ser-Asp-Lys-Pro in hypertension-induced target organ damage. Am. J. Physiol. Heart Circ. Physiol., 2008, 294(3), H1226-H1232.
[http://dx.doi.org/10.1152/ajpheart.00305.2007] [PMID: 18178715]
[22]
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.; Bernstein, K.E. Rediscovering ACE: novel insights into the many roles of the angiotensin-converting enzyme. J. Mol. Med. (Berl.), 2013, 91(10), 1143-1154.
[http://dx.doi.org/10.1007/s00109-013-1051-z] [PMID: 23686164]
[23]
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. A modern understanding of the traditional and nontraditional biological functions of angiotensin-converting enzyme. Pharmacol. Rev., 2012, 65(1), 1-46.
[http://dx.doi.org/10.1124/pr.112.006809] [PMID: 23257181]
[24]
Kumar, N.; Yin, C. The anti-inflammatory peptide Ac-SDKP: Synthesis, role in ACE inhibition, and its therapeutic potential in hypertension and cardiovascular diseases. Pharmacol. Res., 2018, 134, 268-279.
[http://dx.doi.org/10.1016/j.phrs.2018.07.006] [PMID: 29990624]
[25]
Michaud, A.; Williams, T.A.; Chauvet, M.T.; Corvol, P. 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 I. Mol. Pharmacol., 1997, 51(6), 1070-1076.
[http://dx.doi.org/10.1124/mol.51.6.1070] [PMID: 9187274]
[26]
Junot, C.; Menard, J.; Gonzales, M.F.; Michaud, A.; Corvol, P.; Ezan, E. In vivo assessment of captopril selectivity of angiotensin I-converting enzyme inhibition: differential inhibition of acetyl-ser-asp-lys-pro and angiotensin I hydrolysis. J. Pharmacol. Exp. Ther., 1999, 289(3), 1257-1261.
[PMID: 10336514]
[27]
Voronov, S.; Zueva, N.; Orlov, V.; Arutyunyan, A.; Kost, O. Temperature-induced selective death of the C-domain within angiotensin-converting enzyme molecule. FEBS Lett., 2002, 522(1-3), 77-82.
[http://dx.doi.org/10.1016/S0014-5793(02)02888-0] [PMID: 12095622]
[28]
Jaspard, E.; Wei, L.; Alhenc-Gelas, F. 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., 1993, 268(13), 9496-9503.
[PMID: 7683654]
[29]
Natesh, R.; Schwager, S.L.; Sturrock, E.D.; Acharya, K.R. Crystal structure of the human angiotensin-converting enzyme-lisinopril complex. Nature, 2003, 421(6922), 551-554.
[http://dx.doi.org/10.1038/nature01370] [PMID: 12540854]
[30]
Sturrock, E.D.; Natesh, R.; van Rooyen, J.M.; Acharya, K.R. Structure of angiotensin I-converting enzyme. Cell. Mol. Life Sci., 2004, 61(21), 2677-2686.
[http://dx.doi.org/10.1007/s00018-004-4239-0] [PMID: 15549168]
[31]
Acharya, K.R.; Sturrock, E.D.; Riordan, J.F.; Ehlers, M.R. Ace revisited: a new target for structure-based drug design. Nat. Rev. Drug Discov., 2003, 2(11), 891-902.
[http://dx.doi.org/10.1038/nrd1227] [PMID: 14668810]
[32]
Spyranti, Z.; Galanis, A.S.; Pairas, G.; Spyroulias, G.A.; Manessi-Zoupa, E.; Cordopatis, P. Synthetic peptides as structural maquettes of Angiotensin-I converting enzyme catalytic sites. Bioinorg. Chem. Appl., 2010.820476
[http://dx.doi.org/10.1155/2010/820476] [PMID: 20634989]
[33]
Natesh, R.; Schwager, S.L.; Evans, H.R.; Sturrock, E.D.; Acharya, K.R. Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme. Biochemistry, 2004, 43(27), 8718-8724.
[http://dx.doi.org/10.1021/bi049480n] [PMID: 15236580]
[34]
Watermeyer, J.M.; Kröger, W.L.; O’Neill, H.G.; Sewell, B.T.; Sturrock, E.D. Probing the basis of domain-dependent inhibition using novel ketone inhibitors of Angiotensin-converting enzyme. Biochemistry, 2008, 47(22), 5942-5950.
[http://dx.doi.org/10.1021/bi8002605] [PMID: 18457420]
[35]
Watermeyer, J.M.; Kröger, W.L.; O’Neill, H.G.; Sewell, B.T.; Sturrock, E.D. Characterization of domain-selective inhibitor binding in angiotensin-converting enzyme using a novel derivative of lisinopril. Biochem. J., 2010, 428(1), 67-74.
[http://dx.doi.org/10.1042/BJ20100056] [PMID: 20233165]
[36]
Akif, M.; Schwager, S.L.; Anthony, C.S.; Czarny, B.; Beau, F.; Dive, V.; Sturrock, E.D.; Acharya, K.R. Novel mechanism of inhibition of human angiotensin-I-converting enzyme (ACE) by a highly specific phosphinic tripeptide. Biochem. J., 2011, 436(1), 53-59.
[http://dx.doi.org/10.1042/BJ20102123] [PMID: 21352096]
[37]
Akif, M.; Masuyer, G.; Schwager, S.L.; Bhuyan, B.J.; Mugesh, G.; Isaac, R.E.; Sturrock, E.D.; Acharya, K.R. Structural characterization of angiotensin I-converting enzyme in complex with a selenium analogue of captopril. FEBS J., 2011, 278(19), 3644-3650.
[http://dx.doi.org/10.1111/j.1742-4658.2011.08276.x] [PMID: 21810173]
[38]
Masuyer, G.; Schwager, S.L.; Sturrock, E.D.; Isaac, R.E.; Acharya, K.R. Molecular recognition and regulation of human angiotensin-I converting enzyme (ACE) activity by natural inhibitory peptides. Sci. Rep., 2012, 2, 717.
[http://dx.doi.org/10.1038/srep00717] [PMID: 23056909]
[39]
Masuyer, G.; Akif, M.; Czarny, B.; Beau, F.; Schwager, S.L.; Sturrock, E.D.; Isaac, R.E.; Dive, V.; Acharya, K.R. Crystal structures of highly specific phosphinic tripeptide enantiomers in complex with the angiotensin-I converting enzyme. FEBS J., 2014, 281(3), 943-956.
[http://dx.doi.org/10.1111/febs.12660] [PMID: 24289879]
[40]
Kramer, G.J.; Mohd, A.; Schwager, S.L.U.; Masuyer, G.; Acharya, K.R.; Sturrock, E.D.; Bachmann, B.O. Interkingdom pharmacology of Angiotensin-I converting enzyme inhibitor phosphonates produced by actinomycetes. ACS Med. Chem. Lett., 2014, 5(4), 346-351.
[http://dx.doi.org/10.1021/ml4004588] [PMID: 24900839]
[41]
Cozier, G.E.; Schwager, S.L.; Sharma, R.K.; Chibale, K.; Sturrock, E.D.; Acharya, K.R. Crystal structures of sampatrilat and sampatrilat-Asp in complex with human ACE - a molecular basis for domain selectivity. FEBS J., 2018, 285(8), 1477-1490.
[http://dx.doi.org/10.1111/febs.14421] [PMID: 29476645]
[42]
Cozier, G.E.; Arendse, L.B.; Schwager, S.L.; Sturrock, E.D.; Acharya, K.R. Molecular basis for multiple omapatrilat binding sites within the ACE C-domain: Implications for drug design. J. Med. Chem., 2018, 61(22), 10141-10154.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01309] [PMID: 30372620]
[43]
Corradi, H.R.; Schwager, S.L.; Nchinda, A.T.; Sturrock, E.D.; Acharya, K.R. Crystal structure of the N-domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design. J. Mol. Biol., 2006, 357(3), 964-974.
[http://dx.doi.org/10.1016/j.jmb.2006.01.048] [PMID: 16476442]
[44]
Anthony, C.S.; Corradi, H.R.; Schwager, S.L.; Redelinghuys, P.; Georgiadis, D.; Dive, V.; Acharya, K.R.; Sturrock, E.D. 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., 2010, 285(46), 35685-35693.
[http://dx.doi.org/10.1074/jbc.M110.167866] [PMID: 20826823]
[45]
Corradi, H.R.; Chitapi, I.; Sewell, B.T.; Georgiadis, D.; Dive, V.; Sturrock, E.D.; Acharya, K.R. The structure of testis angiotensin-converting enzyme in complex with the C domain-specific inhibitor RXPA380. Biochemistry, 2007, 46(18), 5473-5478.
[http://dx.doi.org/10.1021/bi700275e] [PMID: 17439247]
[46]
Douglas, R.G.; Sharma, R.K.; Masuyer, G.; Lubbe, L.; Zamora, I.; Acharya, K.R.; Chibale, K.; Sturrock, E.D. Fragment-based design for the development of N-domain-selective angiotensin-1-converting enzyme inhibitors. Clin. Sci. (Lond.), 2014, 126(4), 305-313.
[http://dx.doi.org/10.1042/CS20130403] [PMID: 24015848]
[47]
Masuyer, G.; Douglas, R.G.; Sturrock, E.D.; Acharya, K.R. Structural basis of Ac-SDKP hydrolysis by Angiotensin-I converting enzyme. Sci. Rep., 2015, 5, 13742.
[http://dx.doi.org/10.1038/srep13742] [PMID: 26403559]
[48]
Fienberg, S.; Cozier, G.E.; Acharya, K.R.; Chibale, K.; Sturrock, E.D. The design and development of a potent and selective novel diprolyl derivative that binds to the N-domain of angiotensin-i converting enzyme. J. Med. Chem., 2018, 61(1), 344-359.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01478] [PMID: 29206036]
[49]
Coates, D.; Isaac, R.E.; Cotton, J.; Siviter, R.; Williams, T.A.; Shirras, A.; Corvol, P.; Dive, V. Functional conservation of the active sites of human and Drosophila angiotensin I-converting enzyme. Biochemistry, 2000, 39(30), 8963-8969.
[http://dx.doi.org/[https://doi.org/10.1021/bi000593q] [PMID: 10913309]
[50]
Kim, H.M.; Shin, D.R.; Yoo, O.J.; Lee, H.; Lee, J.O. Crystal structure of Drosophila angiotensin I-converting enzyme bound to captopril and lisinopril. FEBS Lett., 2003, 538(1-3), 65-70.
[http://dx.doi.org/10.1016/S0014-5793(03)00128-5] [PMID: 12633854]
[51]
Akif, M.; Georgiadis, D.; Mahajan, A.; Dive, V.; Sturrock, E.D.; Isaac, R.E.; Acharya, K.R. High-resolution crystal structures of Drosophila melanogaster angiotensin-converting enzyme in complex with novel inhibitors and antihypertensive drugs. J. Mol. Biol., 2010, 400(3), 502-517.
[http://dx.doi.org/10.1016/j.jmb.2010.05.024] [PMID: 20488190]
[52]
Akif, M.; Ntai, I.; Sturrock, E.D.; Isaac, R.E.; Bachmann, B.O.; Acharya, K.R. Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (AnCE) from Drosophila melanogaster. Biochem. Biophys. Res. Commun., 2010, 398(3), 532-536.
[http://dx.doi.org/10.1016/j.bbrc.2010.06.113] [PMID: 20599761]
[53]
Akif, M.; Masuyer, G.; Bingham, R.J.; Sturrock, E.D.; Isaac, R.E.; Acharya, K.R. Structural basis of peptide recognition by the angiotensin-1 converting enzyme homologue AnCE from Drosophila melanogaster. FEBS J., 2012, 279(24), 4525-4534.
[http://dx.doi.org/10.1111/febs.12038] [PMID: 23082758]
[54]
Harrison, C.; Acharya, K.R. A new high-resolution crystal structure of the Drosophila melanogaster angiotensin converting enzyme homologue, AnCE. FEBS Open Bio, 2015, 5, 661-667.
[http://dx.doi.org/10.1016/j.fob.2015.08.004] [PMID: 26380810]
[55]
Anthony, C.S.; Masuyer, G.; Sturrock, E.D.; Acharya, K.R. Structure based drug design of angiotensin-I converting enzyme inhibitors. Curr. Med. Chem., 2012, 19(6), 845-855.
[http://dx.doi.org/10.2174/092986712799034950] [PMID: 22214449]
[56]
Stoičkov, V.; Šarić, S.; Golubović, M.; Zlatanović, D.; Krtinić, D.; Dinić, L.; Mladenović, B.; Sokolović, D.; Veselinović, A.M. Development of non-peptide ACE inhibitors as novel and potent cardiovascular therapeutics: An in silico modelling approach. SAR QSAR Environ. Res., 2018, 29(7), 503-515.
[http://dx.doi.org/10.1080/1062936X.2018.1485737] [PMID: 30058413]
[57]
Hooper, N.M.; Karran, E.H.; Turner, A.J. Membrane protein secretases. Biochem. J., 1997, 321(Pt 2), 265-279.
[http://dx.doi.org/10.1042/bj3210265] [PMID: 9020855]
[58]
Conrad, N.; Schwager, S.L.; Carmona, A.K.; Sturrock, E.D. The effect of structural motifs on the ectodomain shedding of human angiotensin-converting enzyme. Biochem. Biophys. Res. Commun., 2016, 481(1-2), 111-116.
[http://dx.doi.org/10.1016/j.bbrc.2016.10.155] [PMID: 27818199]
[59]
Pang, S.; Chubb, A.J.; Schwager, S.L.; Ehlers, M.R.; Sturrock, E.D.; Hooper, N.M. Roles of the juxtamembrane and extracellular domains of angiotensin-converting enzyme in ectodomain shedding. Biochem. J., 2001, 358(Pt 1), 185-192.
[http://dx.doi.org/10.1042/bj3580185] [PMID: 11485566]
[60]
Ehlers, M.R.; Riordan, J.F. Angiotensin-converting enzyme: New concepts concerning its biological role. Biochemistry, 1989, 28(13), 5311-5318.
[http://dx.doi.org/10.1021/bi00439a001] [PMID: 2476171]
[61]
O’Neill, H.G.; Redelinghuys, P.; Schwager, S.L.; Sturrock, E.D. The role of glycosylation and domain interactions in the thermal stability of human angiotensin-converting enzyme. Biol. Chem., 2008, 389(9), 1153-1161.
[http://dx.doi.org/10.1515/BC.2008.131] [PMID: 18713002]
[62]
Brás, N.E.; Fernandes, P.A.; Ramos, M.J. QM/MM Study and MD Simulations on the Hypertension Regulator Angiotensin-Converting Enzyme. ACS Catal., 2014, 4(8), 2587-2597.
[http://dx.doi.org/10.1021/cs500093h]
[63]
Tzakos, A.G.; Galanis, A.S.; Spyroulias, G.A.; Cordopatis, P.; Manessi-Zoupa, E.; Gerothanassis, I.P. 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., 2003, 16(12), 993-1003.
[http://dx.doi.org/10.1093/protein/gzg122] [PMID: 14983080]
[64]
Masuyer, G.; Yates, C.J.; Sturrock, E.D.; Acharya, K.R. Angiotensin-I converting enzyme (ACE): structure, biological roles, and molecular basis for chloride ion dependence. Biol. Chem., 2014, 395(10), 1135-1149.
[http://dx.doi.org/10.1515/hsz-2014-0157] [PMID: 25205727]
[65]
Schechter, I.; Berger, A. On the size of the active site in proteases. I. Papain. Biochem. Biophys. Res. Commun., 1967, 27(2), 157-162.
[http://dx.doi.org/10.1016/S0006-291X(67)80055-X] [PMID: 6035483]
[66]
Piepho, R.W. Overview of the angiotensin-converting-enzyme inhibitors. Am. J. Health Syst. Pharm., 2000, 57(Suppl. 1), S3-S7.
[http://dx.doi.org/10.1093/ajhp/57.suppl_1.S3] [PMID: 11030016]
[67]
Regulska, K.; Stanisz, B.; Regulski, M.; Murias, M. How to design a potent, specific, and stable angiotensin-converting enzyme inhibitor. Drug Discov. Today, 2014, 19(11), 1731-1743.
[http://dx.doi.org/10.1016/j.drudis.2014.06.026] [PMID: 24997281]
[68]
Nchinda, A.T.; Chibale, K.; Redelinghuys, P.; Sturrock, E.D. Synthesis of novel keto-ACE analogues as domain-selective angiotensin I-converting enzyme inhibitors. Bioorg. Med. Chem. Lett., 2006, 16(17), 4612-4615.
[http://dx.doi.org/10.1016/j.bmcl.2006.06.003] [PMID: 16784850]
[69]
Kröger, W.L.; Douglas, R.G.; O’Neill, H.G.; Dive, V.; Sturrock, E.D. Investigating the domain specificity of phosphinic inhibitors RXPA380 and RXP407 in angiotensin-converting enzyme. Biochemistry, 2009, 48(35), 8405-8412.
[http://dx.doi.org/10.1021/bi9011226] [PMID: 19658433]
[70]
Harrison, C.; Acharya, K.R. ACE for all - a molecular perspective. J. Cell Commun. Signal., 2014, 8(3), 195-210.
[http://dx.doi.org/10.1007/s12079-014-0236-8] [PMID: 25027949]
[71]
Brew, K. Structure of human ACE gives new insights into inhibitor binding and design. Trends Pharmacol. Sci., 2003, 24(8), 391-394.
[http://dx.doi.org/10.1016/S0165-6147(03)00196-2] [PMID: 12915047]
[72]
Dive, V.; Cotton, J.; Yiotakis, A.; Michaud, A.; Vassiliou, S.; Jiracek, J.; Vazeux, G.; Chauvet, M.T.; Cuniasse, P.; Corvol, P. RXP 407, a phosphinic peptide, is a potent inhibitor of angiotensin I converting enzyme able to differentiate between its two active sites. Proc. Natl. Acad. Sci. USA, 1999, 96(8), 4330-4335.
[http://dx.doi.org/10.1073/pnas.96.8.4330] [PMID: 10200262]
[73]
Junot, C.; Gonzales, M.F.; Ezan, E.; Cotton, J.; Vazeux, G.; Michaud, A.; Azizi, M.; Vassiliou, S.; Yiotakis, A.; Corvol, P.; Dive, V. 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., 2001, 297(2), 606-611.
[PMID: 11303049]
[74]
Georgiadis, D.; Cuniasse, P.; Cotton, J.; Yiotakis, A.; Dive, V. Structural determinants of RXPA380, a potent and highly selective inhibitor of the angiotensin-converting enzyme C-domain. Biochemistry, 2004, 43(25), 8048-8054.
[http://dx.doi.org/10.1021/bi049504q] [PMID: 15209500]
[75]
Lubbe, L.; Sewell, B.T.; Sturrock, E.D. The influence of angiotensin converting enzyme mutations on the kinetics and dynamics of N-domain selective inhibition. FEBS J., 2016, 283(21), 3941-3961.
[http://dx.doi.org/10.1111/febs.13900] [PMID: 27636235]
[76]
Ehlers, M.R. Safety issues associated with the use of angiotensin-converting enzyme inhibitors. Expert Opin. Drug Saf., 2006, 5(6), 739-740.
[http://dx.doi.org/10.1517/14740338.5.6.739] [PMID: 17044798]
[77]
Fuchs, S.; Xiao, H.D.; Cole, J.M.; Adams, J.W.; Frenzel, K.; Michaud, A.; Zhao, H.; Keshelava, G.; Capecchi, M.R.; Corvol, P.; Bernstein, K.E. Role of the N-terminal catalytic domain of angiotensin-converting enzyme investigated by targeted inactivation in mice. J. Biol. Chem., 2004, 279(16), 15946-15953.
[http://dx.doi.org/10.1074/jbc.M400149200] [PMID: 14757757]
[78]
Dive, V.; Chang, C.F.; Yiotakis, A.; Sturrock, E.D. Inhibition of zinc metallopeptidases in cardiovascular disease--from unity to trinity, or duality? Curr. Pharm. Des., 2009, 15(31), 3606-3621.
[http://dx.doi.org/10.2174/138161209789271889] [PMID: 19925415]
[79]
Worthley, M.I.; Corti, R.; Worthley, S.G. Vasopeptidase inhibitors: will they have a role in clinical practice? Br. J. Clin. Pharmacol., 2004, 57(1), 27-36.
[http://dx.doi.org/10.1046/j.1365-2125.2003.01947.x] [PMID: 14678337]
[80]
Jullien, N.; Makritis, A.; Georgiadis, D.; Beau, F.; Yiotakis, A.; Dive, V. Phosphinic tripeptides as dual angiotensin-converting enzyme C-domain and endothelin-converting enzyme-1 inhibitors. J. Med. Chem., 2010, 53(1), 208-220.
[http://dx.doi.org/10.1021/jm9010803] [PMID: 19899765]
[81]
Paulis, L.; Rajkovicova, R.; Simko, F. New developments in the pharmacological treatment of hypertension: Dead-end or a glimmer at the horizon? Curr. Hypertens. Rep., 2015, 17(6), 557.
[http://dx.doi.org/10.1007/s11906-015-0557-x] [PMID: 25893478]
[82]
Campbell, D.J. Vasopeptidase inhibition: A double-edged sword? Hypertension, 2003, 41(3), 383-389.
[http://dx.doi.org/10.1161/01.HYP.0000054215.71691.16] [PMID: 12623931]
[83]
Wallis, E.J.; Ramsay, L.E.; Hettiarachchi, J. Combined inhibition of neutral endopeptidase and angiotensin-converting enzyme by sampatrilat in essential hypertension. Clin. Pharmacol. Ther., 1998, 64(4), 439-449.
[http://dx.doi.org/10.1016/S0009-9236(98)90075-3] [PMID: 9797801]
[84]
Sharma, R.K.; Espinoza-Moraga, M.; Poblete, H.; Douglas, R.G.; Sturrock, E.D.; Caballero, J.; Chibale, K. The dynamic nonprime binding of sampatrilat to the C-domain of angiotensin-converting enzyme. J. Chem. Inf. Model., 2016, 56(12), 2486-2494.
[http://dx.doi.org/10.1021/acs.jcim.6b00524] [PMID: 27959521]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 15
ISSUE: 6
Year: 2019
Page: [574 - 587]
Pages: 14
DOI: 10.2174/1573406415666190514081132
Price: $65

Article Metrics

PDF: 67
HTML: 11
PRC: 1