Matches in SemOpenAlex for { <https://semopenalex.org/work/W2898432987> ?p ?o ?g. }
- W2898432987 abstract "Abstract Falcipains are major haemoglobinases of Plasmodium falciparum required for parasite growth and development. They consist of pro- and mature domains that interact via ‘hot-spot’ interactions and maintain the structural integrity of enzyme in zymogen state. Upon sensing the acidic environment, these interactions dissociate and active enzyme is released. For inhibiting falcipains, several active site inhibitors exist, however, compounds that target via allosteric mechanism remains uncharacterized. Therefore, we designed and synthesized six azapeptide compounds, among which, NA-01 & NA-03 arrested parasite growth by specifically blocking the auto-processing of falcipains. Inhibitors showed high affinity for enzymes in presence of the prodomain without affecting the secondary structure. Binding of NA-03 at the interface induced rigidity in the prodomain preventing structural reorganization. We further reported a histidine-dependent activation of falcipain. Collectively, for the first time we provide a framework for blocking the allosteric site of crucial haemoglobinases of the human malaria parasite. Targeting the allosteric site could provide high selectivity and less vulnerable to drug resistance." @default.
- W2898432987 created "2018-11-02" @default.
- W2898432987 creator A5006635775 @default.
- W2898432987 creator A5023349267 @default.
- W2898432987 creator A5039026034 @default.
- W2898432987 creator A5062965672 @default.
- W2898432987 creator A5069426282 @default.
- W2898432987 creator A5069645446 @default.
- W2898432987 creator A5076833830 @default.
- W2898432987 creator A5084288810 @default.
- W2898432987 creator A5085898035 @default.
- W2898432987 creator A5088808926 @default.
- W2898432987 date "2018-11-01" @default.
- W2898432987 modified "2023-10-14" @default.
- W2898432987 title "Allosteric Site Inhibitor Disrupting Auto-Processing of Malarial Cysteine Proteases" @default.
- W2898432987 cites W1966491286 @default.
- W2898432987 cites W1974993327 @default.
- W2898432987 cites W1976176203 @default.
- W2898432987 cites W1976957132 @default.
- W2898432987 cites W1977523860 @default.
- W2898432987 cites W1977724107 @default.
- W2898432987 cites W1981737096 @default.
- W2898432987 cites W1987575637 @default.
- W2898432987 cites W1989031499 @default.
- W2898432987 cites W2006505501 @default.
- W2898432987 cites W2008590973 @default.
- W2898432987 cites W2009972285 @default.
- W2898432987 cites W2021127497 @default.
- W2898432987 cites W2029985793 @default.
- W2898432987 cites W2034213780 @default.
- W2898432987 cites W2034970659 @default.
- W2898432987 cites W2035627524 @default.
- W2898432987 cites W2044172327 @default.
- W2898432987 cites W2048255085 @default.
- W2898432987 cites W2060229787 @default.
- W2898432987 cites W2061831834 @default.
- W2898432987 cites W2063684273 @default.
- W2898432987 cites W2070296093 @default.
- W2898432987 cites W2070828985 @default.
- W2898432987 cites W2075682016 @default.
- W2898432987 cites W2077613620 @default.
- W2898432987 cites W2081327421 @default.
- W2898432987 cites W2081729133 @default.
- W2898432987 cites W2083328485 @default.
- W2898432987 cites W2084527370 @default.
- W2898432987 cites W2085011361 @default.
- W2898432987 cites W2095361639 @default.
- W2898432987 cites W2095460341 @default.
- W2898432987 cites W2096355268 @default.
- W2898432987 cites W2104799919 @default.
- W2898432987 cites W2121234985 @default.
- W2898432987 cites W2124454170 @default.
- W2898432987 cites W2125677289 @default.
- W2898432987 cites W2131316262 @default.
- W2898432987 cites W2143287044 @default.
- W2898432987 cites W2149561634 @default.
- W2898432987 cites W2157017502 @default.
- W2898432987 cites W2167285933 @default.
- W2898432987 cites W2168918061 @default.
- W2898432987 cites W2169230642 @default.
- W2898432987 cites W2170397837 @default.
- W2898432987 cites W2171021060 @default.
- W2898432987 cites W2179482622 @default.
- W2898432987 cites W2326722042 @default.
- W2898432987 cites W2359173335 @default.
- W2898432987 cites W2425507234 @default.
- W2898432987 cites W2542763137 @default.
- W2898432987 cites W2552420307 @default.
- W2898432987 cites W2587090001 @default.
- W2898432987 cites W2593829322 @default.
- W2898432987 cites W2753479285 @default.
- W2898432987 cites W4234645500 @default.
- W2898432987 cites W4248713218 @default.
- W2898432987 doi "https://doi.org/10.1038/s41598-018-34564-8" @default.
- W2898432987 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6212536" @default.
- W2898432987 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30385827" @default.
- W2898432987 hasPublicationYear "2018" @default.
- W2898432987 type Work @default.
- W2898432987 sameAs 2898432987 @default.
- W2898432987 citedByCount "13" @default.
- W2898432987 countsByYear W28984329872019 @default.
- W2898432987 countsByYear W28984329872020 @default.
- W2898432987 countsByYear W28984329872021 @default.
- W2898432987 countsByYear W28984329872022 @default.
- W2898432987 crossrefType "journal-article" @default.
- W2898432987 hasAuthorship W2898432987A5006635775 @default.
- W2898432987 hasAuthorship W2898432987A5023349267 @default.
- W2898432987 hasAuthorship W2898432987A5039026034 @default.
- W2898432987 hasAuthorship W2898432987A5062965672 @default.
- W2898432987 hasAuthorship W2898432987A5069426282 @default.
- W2898432987 hasAuthorship W2898432987A5069645446 @default.
- W2898432987 hasAuthorship W2898432987A5076833830 @default.
- W2898432987 hasAuthorship W2898432987A5084288810 @default.
- W2898432987 hasAuthorship W2898432987A5085898035 @default.
- W2898432987 hasAuthorship W2898432987A5088808926 @default.
- W2898432987 hasBestOaLocation W28984329871 @default.
- W2898432987 hasConcept C166342909 @default.
- W2898432987 hasConcept C181199279 @default.
- W2898432987 hasConcept C182220744 @default.
- W2898432987 hasConcept C185592680 @default.