{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:57:27Z","timestamp":1789037847545,"version":"build-2803163510"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T00:00:00Z","timestamp":1725062400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T00:00:00Z","timestamp":1725062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["NRF-CRP24-2020-005"],"award-info":[{"award-number":["NRF-CRP24-2020-005"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-024-06774-6","type":"journal-article","created":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T07:01:55Z","timestamp":1725087715000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inhibition of falcilysin from Plasmodium falciparum by interference with its closed-to-open dynamic transition"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4336-9003","authenticated-orcid":false,"given":"Jianqing","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6248-2349","authenticated-orcid":false,"given":"Xinfu","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9226-1165","authenticated-orcid":false,"given":"Zara","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong Wai","family":"Liew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3973-686X","authenticated-orcid":false,"given":"Abbas","family":"El Sahili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeniya V.","family":"Pechnikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4331-7000","authenticated-orcid":false,"given":"Peter R.","family":"Preiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9830-8446","authenticated-orcid":false,"given":"Zbynek","family":"Bozdech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7298-0835","authenticated-orcid":false,"given":"Yong-Gui","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9623-8130","authenticated-orcid":false,"given":"Julien","family":"Lescar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,31]]},"reference":[{"key":"6774_CR1","unstructured":"World Health Organization. World Malaria Report 2022."},{"key":"6774_CR2","doi-asserted-by":"publisher","first-page":"S319","DOI":"10.1016\/j.amepre.2015.09.011","volume":"49","author":"SL Hoffman","year":"2015","unstructured":"Hoffman, S. L., Vekemans, J., Richie, T. L. & Duffy, P. E. The march toward malaria vaccines. Am. J. Prev. Med. 49, S319\u2013S333 (2015).","journal-title":"Am. J. Prev. Med."},{"key":"6774_CR3","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1056\/NEJMoa0808859","volume":"361","author":"AM Dondorp","year":"2009","unstructured":"Dondorp, A. M. et al. Artemisinin resistance in Plasmodium falciparum malaria. N. Engl. J. Med. 361, 455\u2013467 (2009).","journal-title":"N. Engl. J. Med."},{"key":"6774_CR4","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1093\/cid\/ciw388","volume":"63","author":"AP Phyo","year":"2016","unstructured":"Phyo, A. P. et al. Declining efficacy of artemisinin combination therapy against P. falciparum malaria on the Thai\u2013Myanmar Border (2003\u20132013): the role of parasite genetic factors. Clin. Infect. Dis. 63, 784\u2013791 (2016).","journal-title":"Clin. Infect. Dis."},{"key":"6774_CR5","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.pt.2016.04.014","volume":"32","author":"ML Hovlid","year":"2016","unstructured":"Hovlid, M. L. & Winzeler, E. A. Phenotypic screens in antimalarial drug discovery. Trends Parasitol. 32, 697\u2013707 (2016).","journal-title":"Trends Parasitol."},{"key":"6774_CR6","doi-asserted-by":"publisher","first-page":"e62906","DOI":"10.1371\/journal.pone.0062906","volume":"8","author":"T Spangenberg","year":"2013","unstructured":"Spangenberg, T. et al. The open access malaria box: a drug discovery catalyst for neglected diseases. PLoS ONE 8, e62906 (2013).","journal-title":"PLoS ONE"},{"key":"6774_CR7","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.chembiol.2019.11.009","volume":"27","author":"JM Murithi","year":"2020","unstructured":"Murithi, J. M. et al. Combining stage specificity and metabolomic profiling to advance antimalarial drug discovery. Cell Chem. Biol. 27, 158\u2013171.e3 (2020).","journal-title":"Cell Chem. Biol."},{"key":"6774_CR8","doi-asserted-by":"publisher","first-page":"6635","DOI":"10.1128\/AAC.01224-16","volume":"60","author":"EL Allman","year":"2016","unstructured":"Allman, E. L., Painter, H. J., Samra, J., Carrasquilla, M. & Llin\u00e1s, M. Metabolomic profiling of the Malaria Box reveals antimalarial target pathways. Antimicrob. Agents Chemother. 60, 6635\u20136643 (2016).","journal-title":"Antimicrob. Agents Chemother."},{"key":"6774_CR9","doi-asserted-by":"publisher","first-page":"2414","DOI":"10.1128\/AAC.05326-11","volume":"56","author":"MA Powles","year":"2012","unstructured":"Powles, M. A. et al. MK-4815, a potential new oral agent for treatment of malaria. Antimicrob. Agents Chemother. 56, 2414\u20132419 (2012).","journal-title":"Antimicrob. Agents Chemother."},{"key":"6774_CR10","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1038\/s41596-020-0310-z","volume":"15","author":"JM Dziekan","year":"2020","unstructured":"Dziekan, J. M. et al. Cellular thermal shift assay for the identification of drug\u2013target interactions in the Plasmodium falciparum proteome. Nat. Protoc. 15, 1881\u20131921 (2020).","journal-title":"Nat. Protoc."},{"key":"6774_CR11","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/j.chembiol.2024.03.002","volume":"31","author":"G Wirjanata","year":"2024","unstructured":"Wirjanata, G. et al. Identification of an inhibitory pocket in falcilysin provides a new avenue for malaria drug development. Cell Chem. Biol. 31, 743\u2013759.e8 (2024).","journal-title":"Cell Chem. Biol."},{"key":"6774_CR12","doi-asserted-by":"publisher","first-page":"eaau3174","DOI":"10.1126\/scitranslmed.aau3174","volume":"11","author":"JM Dziekan","year":"2019","unstructured":"Dziekan, J. M. et al. Identifying purine nucleoside phosphorylase as the target of quinine using cellular thermal shift assay. Sci. Transl. Med. 11, eaau3174 (2019).","journal-title":"Sci. Transl. Med."},{"key":"6774_CR13","doi-asserted-by":"publisher","first-page":"105586","DOI":"10.1016\/j.jbc.2023.105586","volume":"300","author":"Z Chung","year":"2024","unstructured":"Chung, Z. et al. Identification and structural validation of purine nucleoside phosphorylase from Plasmodium falciparum as a target of MMV00848. J. Biol. Chem. 300, 105586 (2024).","journal-title":"J. Biol. Chem."},{"key":"6774_CR14","doi-asserted-by":"publisher","first-page":"32411","DOI":"10.1074\/jbc.274.45.32411","volume":"274","author":"KK Eggleson","year":"1999","unstructured":"Eggleson, K. K., Duffin, K. L. & Goldberg, D. E. Identification and characterization of falcilysin, a metallopeptidase involved in hemoglobin catabolism within the malaria parasite Plasmodium falciparum. J. Biol. Chem. 274, 32411\u201332417 (1999).","journal-title":"J. Biol. Chem."},{"key":"6774_CR15","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/S0166-6851(03)00098-7","volume":"129","author":"CE Murata","year":"2003","unstructured":"Murata, C. E. & Goldberg, D. E. Plasmodium falciparum falcilysin: an unprocessed food vacuole enzyme. Mol. Biochem. Parasitol. 129, 123\u2013126 (2003).","journal-title":"Mol. Biochem. Parasitol."},{"key":"6774_CR16","doi-asserted-by":"publisher","first-page":"38022","DOI":"10.1074\/jbc.M306842200","volume":"278","author":"CE Murata","year":"2003","unstructured":"Murata, C. E. & Goldberg, D. E. Plasmodium falciparum falcilysin: a metalloprotease with dual specificity. J. Biol. Chem. 278, 38022\u201338028 (2003).","journal-title":"J. Biol. Chem."},{"key":"6774_CR17","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1111\/j.1365-2958.2006.05528.x","volume":"63","author":"SA Ralph","year":"2007","unstructured":"Ralph, S. A. Subcellular multitasking\u2014multiple destinations and roles for the Plasmodium falcilysin protease. Mol. Microbiol. 63, 309\u2013313 (2007).","journal-title":"Mol. Microbiol."},{"key":"6774_CR18","doi-asserted-by":"publisher","first-page":"5581","DOI":"10.1021\/acs.chemrev.8b00030","volume":"118","author":"JL Arolas","year":"2018","unstructured":"Arolas, J. L., Goulas, T., Cuppari, A. & Gomis-R\u00fcth, F. X. Multiple architectures and mechanisms of latency in metallopeptidase zymogens. Chem. Rev. 118, 5581\u20135597 (2018).","journal-title":"Chem. Rev."},{"key":"6774_CR19","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/S0969-2126(01)00621-9","volume":"9","author":"AB Taylor","year":"2001","unstructured":"Taylor, A. B. et al. Crystal structures of mitochondrial processing peptidase reveal the mode for specific cleavage of import signal sequences. Structure 9, 615\u2013625 (2001).","journal-title":"Structure"},{"key":"6774_CR20","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1111\/j.1365-2958.2006.05443.x","volume":"63","author":"M Ponpuak","year":"2007","unstructured":"Ponpuak, M. et al. A role for falcilysin in transit peptide degradation in the Plasmodium falciparum apicoplast. Mol. Microbiol. 63, 314\u2013334 (2007).","journal-title":"Mol. Microbiol."},{"key":"6774_CR21","doi-asserted-by":"publisher","first-page":"e80813","DOI":"10.7554\/eLife.80813","volume":"11","author":"RCS Edgar","year":"2022","unstructured":"Edgar, R. C. S. et al. Genetic and chemical validation of Plasmodium falciparum aminopeptidase PfA-M17 as a drug target in the hemoglobin digestion pathway. Elife 11, e80813 (2022).","journal-title":"Elife"},{"key":"6774_CR22","doi-asserted-by":"publisher","first-page":"PR32","DOI":"10.1021\/cr900395y","volume":"110","author":"WA Loughlin","year":"2010","unstructured":"Loughlin, W. A., Tyndall, J. D. A., Glenn, M. P., Hill, T. A. & Fairlie, D. P. Beta-strand mimetics. Chem. Rev. 110, PR32\u2013PR69 (2010).","journal-title":"Chem. Rev."},{"key":"6774_CR23","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1038\/nature05143","volume":"443","author":"Y Shen","year":"2006","unstructured":"Shen, Y., Joachimiak, A., Rich Rosner, M. & Tang, W. J. Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism. Nature 443, 870\u2013874 (2006).","journal-title":"Nature"},{"key":"6774_CR24","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1038\/sj.emboj.7601080","volume":"25","author":"KA Johnson","year":"2006","unstructured":"Johnson, K. A. et al. The closed structure of presequence protease PreP forms a unique 10 000 \u00c53 chamber for proteolysis. EMBO J. 25, 1977\u20131986 (2006).","journal-title":"EMBO J."},{"key":"6774_CR25","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1016\/j.str.2014.05.003","volume":"22","author":"JV King","year":"2014","unstructured":"King, J. V. et al. Molecular basis of substrate recognition and degradation by human presequence protease. Structure 22, 996\u20131007 (2014).","journal-title":"Structure"},{"key":"6774_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-022-29322-4","volume":"13","author":"WG Liang","year":"2022","unstructured":"Liang, W. G. et al. Structural basis for the mechanisms of human presequence protease conformational switch and substrate recognition. Nat. Commun. 13, 1\u201314 (2022).","journal-title":"Nat. Commun."},{"key":"6774_CR27","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1107\/S0907444909047337","volume":"66","author":"W Kabsch","year":"2010","unstructured":"Kabsch, W. XDS. Acta Crystallogr. D 66, 125\u2013132 (2010).","journal-title":"Acta Crystallogr. D"},{"key":"6774_CR28","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1107\/S0021889807021206","volume":"40","author":"AJ McCoy","year":"2007","unstructured":"McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658\u2013674 (2007).","journal-title":"J. Appl. Crystallogr."},{"key":"6774_CR29","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1107\/S0907444912001308","volume":"68","author":"PV Afonine","year":"2012","unstructured":"Afonine, P. V. et al. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr. D 68, 352\u2013367 (2012).","journal-title":"Acta Crystallogr. D"},{"key":"6774_CR30","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1107\/S0907444904019158","volume":"60","author":"P Emsley","year":"2004","unstructured":"Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126\u20132132 (2004).","journal-title":"Acta Crystallogr. D"},{"key":"6774_CR31","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.jsb.2012.09.006","volume":"180","author":"SHW Scheres","year":"2012","unstructured":"Scheres, S. H. W. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519\u2013530 (2012).","journal-title":"J. Struct. Biol."},{"key":"6774_CR32","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.jsb.2015.08.008","volume":"192","author":"A Rohou","year":"2015","unstructured":"Rohou, A. & Grigorieff, N. CTFFIND4: fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216\u2013221 (2015).","journal-title":"J. Struct. Biol."},{"key":"6774_CR33","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ultramic.2013.06.004","volume":"135","author":"S Chen","year":"2013","unstructured":"Chen, S. et al. High-resolution noise substitution to measure overfitting and validate resolution in 3D structure determination by single particle electron cryomicroscopy. Ultramicroscopy 135, 24\u201335 (2013).","journal-title":"Ultramicroscopy"},{"key":"6774_CR34","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/pro.3943","volume":"30","author":"EF Pettersen","year":"2021","unstructured":"Pettersen, E. F. et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci. 30, 70\u201382 (2021).","journal-title":"Protein Sci."},{"key":"6774_CR35","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"PD Adams","year":"2010","unstructured":"Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213\u2013221 (2010).","journal-title":"Acta Crystallogr. D"},{"key":"6774_CR36","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/nmeth.4347","volume":"14","author":"YZ Tan","year":"2017","unstructured":"Tan, Y. Z. et al. Addressing preferred specimen orientation in single-particle cryo-EM through tilting. Nat. Methods 14, 793\u2013796 (2017).","journal-title":"Nat. Methods"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-06774-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-06774-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-06774-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T23:03:22Z","timestamp":1725145402000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-06774-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,31]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["6774"],"URL":"https:\/\/doi.org\/10.1038\/s42003-024-06774-6","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,31]]},"assertion":[{"value":"23 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1070"}}