{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:47:16Z","timestamp":1790243236264,"version":"4.1.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T00:00:00Z","timestamp":1490572800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T00:00:00Z","timestamp":1490572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The control of mosquitoes is threatened by the appearance of insecticide resistance and therefore new control chemicals are urgently required. Here we show that inhibitors of mosquito peptidyl dipeptidase, a peptidase related to mammalian angiotensin-converting enzyme (ACE), are insecticidal to larvae of the mosquitoes, <jats:italic>Aedes aegypti<\/jats:italic> and <jats:italic>Anopheles gambiae.<\/jats:italic> ACE inhibitors (captopril, fosinopril and fosinoprilat) and two peptides (trypsin-modulating oostatic factor\/TMOF and a bradykinin-potentiating peptide, BPP-12b) were all inhibitors of the larval ACE activity of both mosquitoes. Two inhibitors, captopril and fosinopril (a pro-drug ester of fosinoprilat), were tested for larvicidal activity. Within 24\u2009h captopril had killed &gt;90% of the early instars of both species with 3<jats:sup>rd<\/jats:sup> instars showing greater resistance. Mortality was also high within 24\u2009h of exposure of 1<jats:sup>st<\/jats:sup>, 2<jats:sup>nd<\/jats:sup> and 3<jats:sup>rd<\/jats:sup> instars of <jats:italic>An. gambiae<\/jats:italic> to fosinopril. Fosinopril was also toxic to <jats:italic>Ae. aegypti<\/jats:italic> larvae, although the 1<jats:sup>st<\/jats:sup> instars appeared to be less susceptible to this pro-drug even after 72\u2009h exposure. Homology models of the larval <jats:italic>An. gambiae<\/jats:italic> ACE proteins (AnoACE2 and AnoACE3) reveal structural differences compared to human ACE, suggesting that structure-based drug design offers a fruitful approach to the development of selective inhibitors of mosquito ACE enzymes as novel larvicides.<\/jats:p>","DOI":"10.1038\/srep45409","type":"journal-article","created":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T10:14:17Z","timestamp":1490609657000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The toxicity of angiotensin converting enzyme inhibitors to larvae of the disease vectors Aedes aegypti and Anopheles gambiae"],"prefix":"10.1038","volume":"7","author":[{"given":"Zatul-\u2019Iffah","family":"Abu Hasan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur M.","family":"Ismail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidayatulfathi","family":"Othman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyles E.","family":"Cozier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Ravi","family":"Acharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Elwyn","family":"Isaac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,27]]},"reference":[{"key":"BFsrep45409_CR1","doi-asserted-by":"publisher","first-page":"e382","DOI":"10.1371\/journal.pntd.0000382","volume":"3","author":"MA Johansson","year":"2009","unstructured":"Johansson, M. A., Dominici, F. & Glass, G. E. Local and global effects of climate on dengue transmission in Puerto Rico. PLoS Negl Trop Dis 3, e382, doi: 10.1371\/journal.pntd.0000382 (2009).","journal-title":"PLoS Negl Trop Dis"},{"key":"BFsrep45409_CR2","doi-asserted-by":"publisher","first-page":"e1477","DOI":"10.1371\/journal.pntd.0001477","volume":"6","author":"AD Haddow","year":"2012","unstructured":"Haddow, A. D. et al. Genetic characterization of Zika virus strains: geographic expansion of the Asian lineage. PLoS Negl Trop Dis 6, e1477, doi: 10.1371\/journal.pntd.0001477 (2012).","journal-title":"PLoS Negl Trop Dis"},{"key":"BFsrep45409_CR3","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1146\/annurev-ento-112408-085423","volume":"55","author":"A Enayati","year":"2010","unstructured":"Enayati, A. & Hemingway, J. Malaria Management: Past, Present, and Future. Annual Review of Entomology 55, 569\u2013591, doi: 10.1146\/annurev-ento-112408-085423 (2010).","journal-title":"Annual Review of Entomology"},{"key":"BFsrep45409_CR4","doi-asserted-by":"crossref","unstructured":"Hemingway, J. The role of vector control in stopping the transmission of malaria: threats and opportunities. Philos T R Soc B 369, doi: Artn 2013043110.1098\/Rstb.2013.0431 (2014).","DOI":"10.1098\/rstb.2013.0431"},{"key":"BFsrep45409_CR5","doi-asserted-by":"publisher","first-page":"e99822","DOI":"10.1371\/journal.pone.0099822","volume":"9","author":"EK Thomsen","year":"2014","unstructured":"Thomsen, E. K. et al. Underpinning sustainable vector control through informed insecticide resistance management. PLoS One 9, e99822, doi: 10.1371\/journal.pone.0099822 (2014).","journal-title":"PLoS One"},{"key":"BFsrep45409_CR6","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.pt.2015.11.010","volume":"32","author":"H Ranson","year":"2016","unstructured":"Ranson, H. & Lissenden, N. Insecticide Resistance in African Anopheles Mosquitoes: A Worsening Situation that Needs Urgent Action to Maintain Malaria Control. Trends Parasitol 32, 187\u2013196, doi: 10.1016\/j.pt.2015.11.010 (2016).","journal-title":"Trends Parasitol"},{"key":"BFsrep45409_CR7","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1146\/annurev.bi.45.070176.000445","volume":"45","author":"RL Soffer","year":"1976","unstructured":"Soffer, R. L. Angiotensin-converting enzyme and the regulation of vasoactive peptides. Annual Review of Biochemistry 45, 73\u201394 (1976).","journal-title":"Annual Review of Biochemistry"},{"key":"BFsrep45409_CR8","first-page":"345","volume":"56","author":"EG Erdos","year":"1987","unstructured":"Erdos, E. G. & Skidgel, R. A. The angiotensin I-converting enzyme. Lab Invest 56, 345\u2013348 (1987).","journal-title":"Lab Invest"},{"key":"BFsrep45409_CR9","doi-asserted-by":"publisher","first-page":"S 3","DOI":"10.1097\/00004872-199509003-00002","volume":"13","author":"P Corvol","year":"1995","unstructured":"Corvol, P., Michaud, A., Soubrier, F. & Williams, T. A. Recent Advances In Knowledge Of the Structure and Function Of the Angiotensin-I Converting-Enzyme. J. Hypertension 13 , S 3\u2013S 10 (1995).","journal-title":"J. Hypertension"},{"key":"BFsrep45409_CR10","doi-asserted-by":"publisher","first-page":"5484","DOI":"10.1021\/bi00644a014","volume":"16","author":"DW Cushman","year":"1977","unstructured":"Cushman, D. W., Cheung, H. S., Sabo, E. F. & Ondetti, M. A. Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acids. Biochemistry 16, 5484\u20135491 (1977).","journal-title":"Biochemistry"},{"key":"BFsrep45409_CR11","doi-asserted-by":"publisher","first-page":"III134","DOI":"10.1161\/01.HYP.18.5_Suppl.III134","volume":"18","author":"MA Ondetti","year":"1991","unstructured":"Ondetti, M. A. Angiotensin converting enzyme inhibitors. An overview. Hypertension 18, III134\u2013135 (1991).","journal-title":"Hypertension"},{"key":"BFsrep45409_CR12","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1038\/nrd1227","volume":"2","author":"KR Acharya","year":"2003","unstructured":"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 2, 891\u2013902 (2003).","journal-title":"Nat Rev Drug Discov"},{"key":"BFsrep45409_CR13","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/225379a0","volume":"225","author":"SH Ferreira","year":"1970","unstructured":"Ferreira, S. H., Greene, L. J., Alabaste, V. A., Bakhle, Y. S. & Vane, J. R. Activity of Various Fractions of Bradykinin Potentiating Factor against Angiotensin-I Converting Enzyme. Nature 225, 379, doi: 10.1038\/225379a0 (1970).","journal-title":"Nature"},{"key":"BFsrep45409_CR14","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1161\/01.HYP.17.4.589","volume":"17","author":"DW Cushman","year":"1991","unstructured":"Cushman, D. W. & Ondetti, M. A. History of the design of captopril and related inhibitors of angiotensin converting enzyme. Hypertension 17, 589\u2013592 (1991).","journal-title":"Hypertension"},{"key":"BFsrep45409_CR15","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.toxicon.2011.07.013","volume":"59","author":"ACM Camargo","year":"2012","unstructured":"Camargo, A. C. M., Ianzer, D., Guerreiro, J. R. & Serrano, S. M. T. Bradykinin-potentiating peptides: Beyond captopril. Toxicon 59, 516\u2013523, doi: 10.1016\/j.toxicon.2011.07.013 (2012).","journal-title":"Toxicon"},{"key":"BFsrep45409_CR16","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/S0196-9781(96)00232-X","volume":"18","author":"NS Lamango","year":"1997","unstructured":"Lamango, N. S., Nachman, R. J., Hayes, T. K., Strey, A. & Isaac, R. E. Hydrolysis of insect neuropeptides by an angiotensin-converting enzyme from the housefly, Musca domestica . Peptides 18, 47\u201352 (1997).","journal-title":"Peptides"},{"key":"BFsrep45409_CR17","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1042\/bj3140639","volume":"314","author":"NS Lamango","year":"1996","unstructured":"Lamango, N. S., Sajid, M. & Isaac, R. E. The endopeptidase activity and the activation by Cl- of angiotensin- converting enzyme is evolutionarily conserved: purification and properties of an an angiotensin-converting enzyme from the housefly, Musca domestica. Biochem J 314, 639\u2013646 (1996).","journal-title":"Musca domestica. Biochem J"},{"key":"BFsrep45409_CR18","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1016\/S0196-9781(02)00190-0","volume":"23","author":"RJ Siviter","year":"2002","unstructured":"Siviter, R. J. et al. Peptidyl dipeptidases (Ance and Acer) of Drosophila melanogaster: major differences in the substrate specificity of two homologs of human angiotensin I-converting enzyme. Peptides 23, 2025\u20132034 (2002).","journal-title":"Peptides"},{"key":"BFsrep45409_CR19","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1016\/S0196-9781(02)00144-4","volume":"23","author":"A Vandingenen","year":"2002","unstructured":"Vandingenen, A. et al. Isolation and characterization of an angiotensin converting enzyme substrate from vitellogenic ovaries of Neobellieria bullata . Peptides 23, 1853\u20131863 (2002).","journal-title":"Peptides"},{"key":"BFsrep45409_CR20","doi-asserted-by":"publisher","first-page":"3522","DOI":"10.1046\/j.1432-1033.2002.03043.x","volume":"269","author":"K Hens","year":"2002","unstructured":"Hens, K. et al. Characterization of four substrates emphasizes kinetic similarity between insect and human C-domain angiotensin-converting enzyme. Eur J Biochem 269, 3522\u20133530 (2002).","journal-title":"Eur J Biochem"},{"key":"BFsrep45409_CR21","doi-asserted-by":"crossref","unstructured":"Isaac, R. E. & Shirras, A. D. Peptidyl-Dipeptidase A (Invertebrate). Handbook of Proteolytic Enzymes, Vols 1 and 2, 3rd Edition 494\u2013498, doi: 10.1016\/B978-0-12-382219-2.00099-5 (2013).","DOI":"10.1016\/B978-0-12-382219-2.00099-5"},{"key":"BFsrep45409_CR22","doi-asserted-by":"publisher","first-page":"13613","DOI":"10.1074\/jbc.270.23.13613","volume":"270","author":"MJ Cornell","year":"1995","unstructured":"Cornell, M. J. et al. Cloning and expression of an evolutionary conserved single-domain angiotensin converting enzyme from Drosophila melanogaster . J Biol Chem 270, 13613\u201313619 (1995).","journal-title":"J Biol Chem"},{"key":"BFsrep45409_CR23","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1042\/bj3180125","volume":"318","author":"TA Williams","year":"1996","unstructured":"Williams, T. A. et al. Drosophila melanogaster angiotensin I-converting enzyme expressed in Pichia pastoris resembles the C domain of the mammalian homologue and does not require glycosylation for secretion and enzymic activity. Biochem. J. 318, 125\u2013131 (1996).","journal-title":"Biochem. J."},{"key":"BFsrep45409_CR24","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1042\/bj3140639","volume":"314","author":"NS Lamango","year":"1996","unstructured":"Lamango, N. S., Sajid, M. & Isaac, R. E. Purification and properties of an angiotensin- converting enzyme from the housefly, Musca domestica. Biochem. J. 314, 639\u2013646 (1996).","journal-title":"Musca domestica. Biochem. J."},{"key":"BFsrep45409_CR25","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s12079-014-0236-8","volume":"8","author":"C Harrison","year":"2014","unstructured":"Harrison, C. & Acharya, K. R. ACE for all - a molecular perspective. J Cell Commun Signal 8, 195\u2013210, doi: 10.1007\/s12079-014-0236-8 (2014).","journal-title":"J Cell Commun Signal"},{"key":"BFsrep45409_CR26","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/ng2049","volume":"39","author":"VR Chintapalli","year":"2007","unstructured":"Chintapalli, V. R., Wang, J. & Dow, J. A. Using FlyAtlas to identify better Drosophila melanogaster models of human disease. Nat Genet 39, 715\u2013720, doi: ng2049 [pii] 10.1038\/ng2049 (2007).","journal-title":"Nat Genet"},{"key":"BFsrep45409_CR27","doi-asserted-by":"publisher","first-page":"3601","DOI":"10.1242\/jeb.009035","volume":"210","author":"CM Rylett","year":"2007","unstructured":"Rylett, C. M., Walker, M. J., Howell, G. J., Shirras, A. D. & Isaac, R. E. Male accessory glands of Drosophila melanogaster make a secreted angiotensin I-converting enzyme (ANCE), suggesting a role for the peptide-processing enzyme in seminal fluid. J Exp Biol 210, 3601\u20133606 (2007).","journal-title":"J Exp Biol"},{"key":"BFsrep45409_CR28","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1111\/j.1432-1033.1996.0414k.x","volume":"237","author":"G Wijffels","year":"1996","unstructured":"Wijffels, G. et al. Cloning and characterisation of angiotensin-converting enzyme from the dipteran species, Haematobia irritans exigua, and its expression in the maturing male reproductive system. Eur J Biochem 237, 414\u2013423 (1996).","journal-title":"Eur J Biochem"},{"key":"BFsrep45409_CR29","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/S0014-5793(99)00870-4","volume":"455","author":"U Ekbote","year":"1999","unstructured":"Ekbote, U., Coates, D. & Isaac, R. E. A mosquito (Anopheles stephensi) angiotensin I-converting enzyme (ACE) is induced by a blood meal and accumulates in the developing ovary. FEBS Lett 455, 219\u2013222 (1999).","journal-title":"FEBS Lett"},{"key":"BFsrep45409_CR30","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/S0965-1748(03)00105-X","volume":"33","author":"UV Ekbote","year":"2003","unstructured":"Ekbote, U. V., Weaver, R. J. & Isaac, R. E. Angiotensin I-converting enzyme (ACE) activity of the tomato moth, Lacanobia oleracea: changes in levels of activity during development and after copulation suggest roles during metamorphosis and reproduction. Insect Biochem Mol Biol 33, 989\u2013998 (2003).","journal-title":"Insect Biochem Mol Biol"},{"key":"BFsrep45409_CR31","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1002\/arch.1047","volume":"47","author":"A Vandingenen","year":"2001","unstructured":"Vandingenen, A. et al. Captopril, a specific inhibitor of angiotensin converting enzyme, enhances both trypsin and vitellogenin titers in the grey fleshfly Neobellieria bullata . Arch Insect Biochem Physiol 47, 161\u2013167 (2001).","journal-title":"Arch Insect Biochem Physiol"},{"key":"BFsrep45409_CR32","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/S1096-4959(03)00019-8","volume":"134","author":"U Ekbote","year":"2003","unstructured":"Ekbote, U., Looker, M. & Isaac, R. E. ACE inhibitors reduce fecundity in the mosquito, Anopheles stephensi . Comp Biochem Physiol B Biochem Mol Biol 134, 593\u2013598 (2003).","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"key":"BFsrep45409_CR33","doi-asserted-by":"publisher","first-page":"467","DOI":"10.14411\/eje.2003.070","volume":"100","author":"N Macours","year":"2003","unstructured":"Macours, N. et al. Isolation of angiotensin converting enzyme from the testes of Locusta migratoria (Orthoptera). European Journal of Entomology 100, 467\u2013474 (2003).","journal-title":"European Journal of Entomology"},{"key":"BFsrep45409_CR34","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1002\/arch.20023","volume":"57","author":"L Vercruysse","year":"2004","unstructured":"Vercruysse, L. et al. The angiotensin converting enzyme inhibitor captopril reduces oviposition and ecdysteroid levels in Lepidoptera. Arch Insect Biochem Physiol 57, 123\u2013132 (2004).","journal-title":"Arch Insect Biochem Physiol"},{"key":"BFsrep45409_CR35","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.peptides.2006.08.029","volume":"28","author":"RE Isaac","year":"2007","unstructured":"Isaac, R. E. et al. Angiotensin-converting enzyme as a target for the development of novel insect growth regulators. Peptides 28, 153\u2013162 (2007).","journal-title":"Peptides"},{"key":"BFsrep45409_CR36","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.jprot.2012.11.011","volume":"78","author":"JJ Xu","year":"2013","unstructured":"Xu, J. J., Baulding, J. & Palli, S. R. Proteomics of Tribolium castaneum seminal fluid proteins: Identification of an angiotensin-converting enzyme as a key player in regulation of reproduction. J Proteomics 78, 83\u201393, doi: 10.1016\/j.jprot.2012.11.011 (2013).","journal-title":"J Proteomics"},{"key":"BFsrep45409_CR37","doi-asserted-by":"publisher","first-page":"H1351","DOI":"10.1152\/ajpheart.00393.2007","volume":"293","author":"N Basso","year":"2007","unstructured":"Basso, N. et al. Protective effect of long-term angiotensin II inhibition. Am J Physiol Heart Circ Physiol 293, H1351\u20131358, doi: 10.1152\/ajpheart.00393.2007 (2007).","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"BFsrep45409_CR38","doi-asserted-by":"publisher","first-page":"e1005866","DOI":"10.1371\/journal.pgen.1005866","volume":"12","author":"S Kumar","year":"2016","unstructured":"Kumar, S., Dietrich, N. & Kornfeld, K. Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span. PLoS Genet 12, e1005866, doi: 10.1371\/journal.pgen.1005866 (2016).","journal-title":"PLoS Genet"},{"key":"BFsrep45409_CR39","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1002\/Arch.20270","volume":"69","author":"E Lemeire","year":"2008","unstructured":"Lemeire, E., Borovsky, D., Van Camp, J. & Smagghe, G. Effect of Ace Inhibitors and TMOF on Growth, Development, and Trypsin Activity of Larval Spodoptera littoralis. Archives of Insect Biochemistry and Physiology 69, 199\u2013208, doi: 10.1002\/Arch.20270 (2008).","journal-title":"Archives of Insect Biochemistry and Physiology"},{"key":"BFsrep45409_CR40","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1111\/j.1749-6632.1999.tb07904.x","volume":"897","author":"RE Isaac","year":"1999","unstructured":"Isaac, R. E., Ekbote, U., Coates, D. & Shirras, A. D. Insect angiotensin-converting enzyme. A processing enzyme with broad substrate specificity and a role in reproduction. Ann N Y Acad Sci 897, 342\u2013347 (1999).","journal-title":"Ann N Y Acad Sci"},{"key":"BFsrep45409_CR41","doi-asserted-by":"publisher","first-page":"3869","DOI":"10.1242\/Jeb.00602","volume":"206","author":"D Borovsky","year":"2003","unstructured":"Borovsky, D. Trypsin-modulating oostatic factor: a potential new larvicide for mosquito control. Journal of Experimental Biology 206, 3869\u20133875, doi: 10.1242\/Jeb.00602 (2003).","journal-title":"Journal of Experimental Biology"},{"key":"BFsrep45409_CR42","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1016\/j.toxicon.2005.02.017","volume":"45","author":"MA Hayashi","year":"2005","unstructured":"Hayashi, M. A. & Camargo, A. C. The Bradykinin-potentiating peptides from venom gland and brain of Bothrops jararaca contain highly site specific inhibitors of the somatic angiotensin-converting enzyme. Toxicon 45, 1163\u20131170, doi: 10.1016\/j.toxicon.2005.02.017 (2005).","journal-title":"Toxicon"},{"key":"BFsrep45409_CR43","doi-asserted-by":"publisher","first-page":"3015","DOI":"10.1096\/fasebj.4.12.2394318","volume":"4","author":"D Borovsky","year":"1990","unstructured":"Borovsky, D., Carlson, D. A., Griffin, P. R., Shabanowitz, J. & Hunt, D. F. Mosquito oostatic factor: a novel decapeptide modulating trypsin-like enzyme biosynthesis in the midgut. Faseb J 4, 3015\u20133020 (1990).","journal-title":"Faseb J"},{"key":"BFsrep45409_CR44","first-page":"5","volume":"1\u20134","author":"D Borovsky","year":"2011","unstructured":"Borovsky, D. et al. Control of mosquito larvae with TMOF and 60 kDa Cry-4Aa expressed in Pichia pastoris . Pesticdes 1\u20134, 5\u201315 (2011).","journal-title":"Pesticdes"},{"key":"BFsrep45409_CR45","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1186\/1471-2164-6-172","volume":"6","author":"S Burnham","year":"2005","unstructured":"Burnham, S., Smith, J. A., Lee, A. J., Isaac, R. E. & Shirras, A. D. The angiotensin-converting enzyme (ACE) gene family of Anopheles gambiae. BMC Genomics 6, 172, doi: 10.1186\/1471-2164-6-172 (2005).","journal-title":"BMC Genomics"},{"key":"BFsrep45409_CR46","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1093\/bioinformatics\/bti770","volume":"22","author":"K Arnold","year":"2006","unstructured":"Arnold, K., Bordoli, L., Kopp, J. & Schwede, T. The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22, 195\u2013201, doi: 10.1093\/bioinformatics\/bti770 (2006).","journal-title":"Bioinformatics"},{"key":"BFsrep45409_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nprot.2008.197","volume":"4","author":"L Bordoli","year":"2009","unstructured":"Bordoli, L. et al. Protein structure homology modeling using SWISS-MODEL workspace. Nature Protocols 4, 1\u201313, doi: 10.1038\/nprot.2008.197 (2009).","journal-title":"Nature Protocols"},{"key":"BFsrep45409_CR48","doi-asserted-by":"publisher","first-page":"W252","DOI":"10.1093\/nar\/gku340","volume":"42","author":"M Biasini","year":"2014","unstructured":"Biasini, M. et al. SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Research 42, W252\u2013W258, doi: 10.1093\/nar\/gku340 (2014).","journal-title":"Nucleic Acids Research"},{"key":"BFsrep45409_CR49","unstructured":"Akif, M. et al. High-Resolution Crystal Structures of Drosophila melanogaster Angiotensin-Converting Enzyme in Complex with Novel Inhibitors and Antihypertensive Drugs. J Mol Biol, doi: S0022-2836(10)00503-6 [pii]10.1016\/j.jmb.2010.05.024 (2010)."},{"key":"BFsrep45409_CR50","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.bbrc.2010.06.113","volume":"398","author":"M Akif","year":"2010","unstructured":"Akif, M. et al. Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (AnCE) from Drosophila melanogaster. Biochem Biophys Res Commun 398, 532\u2013536, doi: S0006-291X(10)01253-2 [pii]10.1016\/j.bbrc.2010.06.113 (2010).","journal-title":"Biochem Biophys Res Commun"},{"key":"BFsrep45409_CR51","doi-asserted-by":"crossref","unstructured":"Masuyer, G., Schwager, S. L. U., 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-Uk 2, doi: 10.1038\/Srep00717 (2012).","DOI":"10.1038\/srep00717"},{"key":"BFsrep45409_CR52","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1042\/BJ20102123","volume":"436","author":"M Akif","year":"2011","unstructured":"Akif, M. et al. Novel mechanism of inhibition of human angiotensin-I-converting enzyme (ACE) by a highly specific phosphinic tripeptide. Biochem J 436, 53\u201359, doi: 10.1042\/BJ20102123 (2011).","journal-title":"Biochem J"},{"key":"BFsrep45409_CR53","doi-asserted-by":"publisher","first-page":"3568","DOI":"10.1074\/jbc.M110.167866","volume":"285","author":"CS Anthony","year":"2010","unstructured":"Anthony, C. S. et al. 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, 3568\u20133593, doi: 10.1074\/jbc.M110.167866 (2010).","journal-title":"J Biol Chem"},{"key":"BFsrep45409_CR54","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1016\/j.jmb.2006.01.048","volume":"357","author":"HR Corradi","year":"2006","unstructured":"Corradi, H. R., Schwager, S. L. U., 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. Journal of Molecular Biology 357, 964\u2013974, doi: 10.1016\/j.jmb.2006.01.048 (2006).","journal-title":"Journal of Molecular Biology"},{"key":"BFsrep45409_CR55","doi-asserted-by":"publisher","first-page":"5473","DOI":"10.1021\/bi700275e","volume":"46","author":"HR Corradi","year":"2007","unstructured":"Corradi, H. R. et al. The structure of testis angiotensin-converting enzyme in complex with the C domain-specific inhibitor RXPA380. Biochemistry 46, 5473\u20135478, doi: 10.1021\/bi700275e (2007).","journal-title":"Biochemistry"},{"key":"BFsrep45409_CR56","doi-asserted-by":"publisher","first-page":"8718","DOI":"10.1021\/bi049480n","volume":"43","author":"R Natesh","year":"2004","unstructured":"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 43, 8718\u20138724 (2004).","journal-title":"Biochemistry"},{"key":"BFsrep45409_CR57","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/nature01370","volume":"421","author":"R Natesh","year":"2003","unstructured":"Natesh, R., Schwager, S. L., Sturrock, E. D. & Acharya, K. R. Crystal structure of the human angiotensin-converting enzyme-lisinopril complex. Nature 421, 551\u2013554 (2003).","journal-title":"Nature"},{"key":"BFsrep45409_CR58","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1046\/j.1432-1327.1998.2570599.x","volume":"257","author":"X Houard","year":"1998","unstructured":"Houard, X. et al. The Drosophila melanogaster-related angiotensin-I-converting enzymes Acer and Ance-distinct enzymic characteristics and alternative expression during pupal development. Eur J Biochem 257, 599\u2013606 (1998).","journal-title":"Eur J Biochem"},{"key":"BFsrep45409_CR59","unstructured":"The PyMOL Molecular Graphics System Version 1.8 Schr\u00f6dinger, LLC."},{"key":"BFsrep45409_CR60","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1107\/S0907444911007281","volume":"67","author":"S McNicholas","year":"2011","unstructured":"McNicholas, S., Potterton, E., Wilson, K. S. & Noble, M. E. M. Presenting your structures: the CCP4mg molecular-graphics software. Acta Crystallogr D 67, 386\u2013394, doi: 10.1107\/S0907444911007281 (2011).","journal-title":"Acta Crystallogr D"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep45409.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep45409","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/srep45409","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/www.nature.com\/articles\/srep45409.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T23:35:12Z","timestamp":1671838512000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep45409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,27]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,6,19]]}},"alternative-id":["BFsrep45409"],"URL":"https:\/\/doi.org\/10.1038\/srep45409","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,27]]},"assertion":[{"value":"3 January 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"45409"}}