
dendrotoxin

neuronukalile volteju gated pottasyam chaanalukalude prathyeka upavibhaagangale thadayunna mamba paambukal ("dendrospies") ulppaadippikkunna presignaptic neurotoxinukalude oru vibhagamaanu dendrotoxinukal, athuvazhi neuro muscular jangshanukalil asattailkolin purathuvidunnathu vardhippikkunnu. pottasyam chaanalukalude uyarnna shakthiyum thiranjedukkalum kaaranam, eee ayoon chaanal proteinukalude ghadanayum pravartthanavum padikkunnathinulla pharmacological upakaranangalayi dendrotoxinukal valare upayogapradamaanennu theliyikkappettittund.
naadeevyavasthayile pravarthanaparamaaya phalangal.
neuronal tissuevile volteju gated pottasyam (keey +) chaanalukalude prathyeka upavibhaagangale dendrotoxinukal thadayunnathaayi theliyikkappettittund. naadeevyavasthayil, volteju gated keey + chaanalukal vishrama membran pottensial niyanthrikkunnathiloode aakshan pottanshyalukalil membron repolarise cheiyunnathiloodeyum njarambukaludeyum peshikaludeyum avesham niyanthrikkunnu. motor neuronukalude ranviyarinte nodukale bandhippikkanum eee pottasyam chaanalukalude pravartthanatthe thadayaanum dendrotoxin sahaayikkumenn theliyikkappettittund. eee reethiyil, dendrotoxinukal pravartthana sheshiyude dairkhyam vardhippikkukayum neuro muscular junctionil asattailkolin release vardhippikkukayum cheiyunnu, ithu peshikalude hyperrexitabilit kanvalseevu lakshanangalkkum kaaranamaayekkam.
dendrotoxin ghadana.
ekadesham 57-60 amino aasidukalude orotta pepttaid shringhala adangiyirikkunna ~ 7kda proteinukalaanu dendrotoxinukal. alfa-dendrotoxinte niravadhi homologukal verthiricheduthittundu, avayellaam alpam vyathyasthamaaya kramathilaanu. ennirunnaalum, eee proteinukalude tanmatra vaasthuvidya madakkal roopeekaranavum valare samaanamaan. dendrotoxinukalkku pepttaidinte enn-terminasinu sameepam valare hrasvamaaya 310-helix undu, athesamayam sii-terminasinu sameepam rund teenn alfa-helix sambhavikkunnu. rund-stranded aantipaarallal β-sheett tanmatra gadanayude madhyabhagam ulkkollunnu. proteente binding pravarthanatthinu pradhaanamaanennu karuthappedunna oru valachodicha β-teenn mekhalayaanu eee rund β-straandukalum bandhippichirikkunnathu. ellah dendrotoxinukalum moonnu disulfide paalangalal cross-link cheythirikkunnu, ithu protein sthiratha nalkukayum athinte gadanaaparamaaya roopeekaranathinu valareyadhikam sambhavana nalkukayum cheiyunnu. eee disulfide bondukal roopappeduthunna sisttain avashishtangal dendrotoxin kudumbatthile ellah amgangalkkidayilum samrakshikkappettittund, avaa c7-c57, c16-c40, c32-c53 (alfa-dendrotoxin anusarichu numpering) ennividangalilaanu sthithicheyyunnathu.
bovin pancreatic tripsin inhibittar (bii. pii. tii. aii) ulppedeyulla kunitts-type serin protees inhibittarukalumaayi gadanaaparamaayi samaanamaan dendrotoxinukal. alfa-dendrotoxin bii. pii. tii. aikkum 35 sathamaanam sequence identityum samanamaaya disulfide bondukalum undennu theliyikkappettittund. eee rund proteinukalum thammilulla gadanaaparamaaya samaroopatha undaayirunnittum, dendrotoxinukal bii. pii. tii. aii polulla alakkaavunna inhibittari protees pravarthanangalonnum prakadippikkunnillenna thonnunnu. bii. pii. tii. aiyil kaanunna protees pravarthanatthinu aavashyamaaya pradhana edapedalukale thadassappeduthunna gadanaaparamaaya vyathyaasangal srishtikkunna pradhana amino assid avashishtangalude abhavam moolamaanu eee pravartthana nashtam undaakunnathenn thonnunnu.
neutral piechil undaakumbol nettu positteev charge ulla adisthaana proteinukalaanu dendrotoxinukal. dendrotoxinukalude positteev charjju cheytha amino assid avashishtangalil bhooribhaagavum gadanayude thaazhathe bhagathaanu sthithicheyyunnathu, ithu proteente oru vashath oru catanic domaine srishtikkunnu. proteininte moonnu praadhamika pradeshangalil kendreekarichirikkunna lysine (lies), arjinin (aarji) avashishtangalil ninnulla positteev charge falangal enn-terminasinu sameepam (aarji 3, aarji 4, lies 5), sii-terminasinu sameepam (aarji 54, aarji 55), idungiya β-teenn mekhalayil (lies 28, lies 29, lies 30). pottasyam chaanalukalude sushirangalile ionic sittukalumaayi (negatteevu charjju cheytha amino aasidukal) prathipravartthikkaan saadyathayullathinaal eee positteev charjju cheytha avashishtangalkk dendrotoxin binding pravartthanatthil nirnaayaka punk vahikkaan kazhiyumennu vishwasikkappedunnu.
jaiva pravartthanangal.
farmacology.
orotta dendrotoxin thanmatra athinte prathirodha prabhavam cheluthunnathinaayi oru pottasyam chaanalumayi vipareethamaayi bandhappedunnu. dendrotoxinte catanic domainile positteev charjju cheytha amino assid avashishtangalum ayoon chaanal sushirathile negatteevu charjju cheytha avashishtangalum thammilulla sthiramaaya electrostaattik edapedalukaliloodeyaanu eee edapedal madhyasthatha vahikkunnathenn nirddeshikkappedunnu. mattu kaatteshan-selective chanalukalkk samaanamaayi pottasyam chanalukalkk, chaanal sushirangal thurakkunnathinu munbu negatteevu chaarjukalude oru meghamundennu vishwasikkappedunnu, ithu pottasyam ayonukale permission paathayiloode vahikkaan sahayikkunnu. oru dendrotoxin thanmathrakal chaanalinte extra sellular uparithalathinaduthulla ionic sittukalumaayi bandhippikkukayum sushirangale shaareerikamaayi thadayukayum athuvazhi ayoon chalakatha thadayukayum cheiyunnuvennu pothuve vishwasikkappedunnu (theliyikkappettillettil). ennirunnaalum, deltta-dendrotoxin avarude taargett proteinukalil oru oof-sentar binding saitt undayirikkaamennum sushirathe shaareerikamaayi thadayunnathinupakaram chaanalinte ghadanayil maattam varuthunnathiloode chaanaline thadassappeduthumennum imredy mckinnonum nirddeshichittundu.
jaivashaasthraparamaayi pradhanappetta avashishtangal.
dendrotoxinukalude pravartthanatthe avayude pottasyam chaanal lakshyangalumayi bandhippikkunnathin eathokke amino assid avashishtangalaan pradhaanamenn thirichariyaan pala padanangalum sramichittundu. harvy mattullavarum. dendrotoxin-aiyude thadayal pravarthanatthinu nirnayakamaaya positteev charjju cheytha avashishtangal thirichariyaan avashishta-nirddishta parishkkaranangal upayogichu. enn-terminal mekhalaykku sameepamulla lies5-nteyum beetaa-teenn mekhalayile lies29-nteyum asattileshan dtx-aii binding afinittiyil ganyamaaya kuravinu kaaranamaayathaayi avar report cheythu. positteev charjju cheytha lysine, arjinin avashishtangal neutral alanainukalkk pakaramaayi saitt directed mutagenesis upayogichu dendrotoxin-keey upayogichum samanamaaya phalangal kaanichittundu. eee phalangal, mattu palathinum oppam, enn-terminal pakuthiyile positteev charjju cheytha laisinukal, prathyekichu 310-helixile lies 5, dendrotoxin avayude pottasyam chaanal lakshyangalumayi bandhippikkunnathil valare pradhana punk vahikkunnuvennu soochippikkunnu. β-teenn mekhalayile lysine avashishtangal kooduthal aashayakkuzhappamundaakkunna phalangal nalkiyittundu, chila dendrotoxin homologukalil ithu jaivashaasthraparamaayi nirnaayakamaanennum mattullavaykku aavasyamillennum thonnunnu. koodaathe, alfa-dtxile muzhuvan lysine trippletinteyum (keey28-keey29-keey30) aalaa-alaa-glylekkulla parivartthanam jaiva pravartthanatthil valare cheria maattathinu kaaranamaayi.
enn-terminasinaduthulla samrakshitha lysine avashishtangal (alfa-dtxil lies5) ellah dendrotoxinukaludeyum jaiva pravarthanatthinu nirnaayakamaanennu pothuvaaya oru daaranayundu, athesamayam beetta-teenn mekhalayile adhika avashishtangal, vyakthigatha vishavasthukkalude edapedalukal avarude vyakthigatha lakshyasthaanangalilekk madhyasthatha vahikkunnathiloode dendrotoxin nirddishtathayil oru punk vahichekkaam. ithu volteju gated keey + chaanalukalude vividha upavibhagangalkkaayi chila dendrotoxinukalude karsanamaaya prathyekatha vishadeekarikkaan sahayikkuka mathramalla, saadhaarana keey + chaanalukalkulla dendrotoxinukalude shakthiyile vyathyasangalkkum kaaranamaakunnu. udaaharanathinu, wang thudangiyava. dendrotoxin-keey-yude kv1.1-maayi edapedunnathu enn-terminasilum β-teenn mekhalayilum ulla lysine avashishtangalaal madhyasthatha vahikkunnuvennum athesamayam alfa-dendrotoxin athinte lakshyavumayi enn-terminasiloode maathram edapedunnuvennum kaanichu. dendrotoxin-keey kv1.1-nuu karsanamaayi thiranjedukkumbol alfa-dendrotoxin kuranja vivechanamullathu enthukondaanennu vishadeekarikkaan eee vipulamaaya interactive domaine sahaayichekkam.
gaveshanathil upayogikkunnu.
kasherukkal adangiya neuronukalude pottasyam chaanalukal uyarnna alavilulla vaividhyam pradarshippikkunnu, ithu pottasyam chaanal sabyoonittukalude vyathyastha kombineshanukalude aavishkaarathiloode neuronukale avayude electrical signalling gunangal krithyamaayi tyoon cheyyaan anuvadikkunnu. koodaathe, avaa jaiva stharangaliludaneelam ionic fluxes niyanthrikkunnathinaal, sellular niyanthranathinteyum vividha kosha tharangalude signal transductionteyum pala vashangalilum avaa pradhaanamaan. athinaal, paambukal, thelukal, kadal anemonukal, koonn ochukal thudangiya jeevikalil ninnulla vaividhyamaarnna sakthamaaya jaiva vishavasthukkalude lakshyamaanu volteju gated pottasyam chaanalukal. athinaal, visham shudheekarikkunnathu pottasyam chaanalukalekkurichulla padanatthinu upayogapradamaaya aushadha upakaranangalayi marria dendrotoxinukal polulla pepttaid vishavasthukkale verthirikkunnathilekku nayichu. vividha tharam pottasyam chaanalukalude shakthiyum thiranjedukkalum kaaranam, eee proteinukalude gadanaaparavum pravarthanaparavumaaya padanatthinu dendrotoxinukal tanmatra probukalaayi upayogapradamaayi. vyakthigatha chaanal tharangal vahikkunna pankukalekkurichulla nammude dhaarana mechappeduthunnathinum eee vaividhyamaarnna chaanal tharangalude pharmacological vargeekaranathinu sahayikkunnathinum ithu sahaayichekkam. koodaathe, radiolabeld dendrotoxinukalude labhyatha kadal anaemonukalile pottasyam chaanal toxinukalude calicludine klaas polulla puthiya pottasyam chaanal toxinukalkkaayulla thirachilil mattu srothassukal parishodhikkunnathinulla oru upakaranam nalkunnu. avasaanamaayi, dendrotoxinukal nalkunna gadanaaparamaaya vivarangal prathyeka tharam pottasyam chaanalukale lakshyamittekkaavunna chikitsa samyukthangalude samanvayathinu soochanakal nalkiyekkaam. vividha binding aseh, chromatography teknikkukal vazhi keey + chaanal protein bandhippikkunna shudheekarikkaanum swabhaava savisheshathakal nalkaanum dendrotoxin aii upayogichittundu.

