"NS10342" . . "mucopolysaccharidosis type III" . "2011-08-08+02:00"^^ . . . . " lysosomal acetyltransferase" . . . . . . "2011-12-31+01:00"^^ . . "Biochemistry and Cell Biology of Human Acetyl-Coenzyme A: Alpha-Glucosaminide N-Acetyltransferase \u2013 Basis for Future Therapeutic Applications in Mucopolysaccharidosis type IIIC"@en . "http://www.isvav.cz/projectDetail.do?rowId=NS10342"^^ . . "Acetyl-koenzym A:glukosaminid N-acetyltransferasa (HGSNAT) katalysuje lysosom\u00E1ln\u00ED odbour\u00E1v\u00E1n\u00ED glykosaminoglykanu heparansulf\u00E1tu. D\u011Bdi\u010Dn\u00FD deficit HGSNAT vede k jeho lysososom\u00E1ln\u00EDmu st\u0159\u00E1d\u00E1n\u00ED a rozvoji klinick\u00E9ho fenotypu mukopolysacharidosy IIIC. Biochemick\u00FDmi a proteomick\u00FDmi p\u0159\u00EDstupy budou charakterizov\u00E1ny partnersk\u00E9 molekuly HGSNAT (proteiny a lipidy), kter\u00E9 mohou sehr\u00E1vat v\u00FDznamnou roli nejen v norm\u00E1ln\u00ED enzymatick\u00E9 funkci HGSNAT, ale i ve vy\u0161\u0161\u00EDm stupni organizace lysosom\u00E1ln\u00EDch membr\u00E1n. Na bun\u011B\u010Dn\u00E9 \u00FArovni bude HGSNAT studov\u00E1na ve smyslu organelov\u00E9 distribuce, lysosom\u00E1ln\u00EDho c\u00EDlen\u00ED, sub-kompartmentalizace v lysosom\u00E1ln\u00EDch membr\u00E1n\u00E1ch a ve vztaz\u00EDch k partnersk\u00FDm molekul\u00E1m (substr\u00E1tu nebo ostatn\u00EDm lysosom\u00E1ln\u00EDm protein\u016Fm). C\u00EDlem projektu je detailn\u00ED charakterizace vlastnost\u00ED, molekul\u00E1rn\u00EDch partner\u016F a nitrobun\u011B\u010Dn\u00E9ho transportu HGSNAT. Na z\u00E1klad\u011B v\u00FDsledk\u016F bude mo\u017En\u00E9 zhodnotit vhodnou strategii pro c\u00EDlen\u00ED HGSNAT do lysosom\u016F pro eventu\u00E1ln\u00ED terapeutick\u00E9 aplikace u MPSIIIC." . "Biochemie a bun\u011B\u010Dn\u00E1 biologie lidsk\u00E9 acetyl-koenzym A : glukosaminid N-acetyltransferasy jako podklad pro budouc\u00ED terapeutick\u00E9 aplikace u mukopolysacharidosy typu IIIC" . . . "Biochemick\u00E9 i mikroskopick\u00E9 studie potvrdily, \u017Ee HGSNAT se nach\u00E1z\u00ED v detergent-rezistentn\u00EDch mikrodom\u00E9n\u00E1ch endosom\u00E1ln\u011B/lysosom\u00E1ln\u00EDho syst\u00E9mu a je transportov\u00E1na nez\u00E1visle na mannosa-6-fosf\u00E1tu, z\u0159ejm\u011B prost\u0159ednictv\u00EDm sortilinu a Rab7A."@cs . . . . "2009-01-01+01:00"^^ . "Multiple biochemical and microscopic studies confirmed that HGSNAT is located in detergent resistand microdomains in endosomal/lysosomal syst\u00E9m, is transported via M6P-independent mechanism most likely involving sortillin and Rab7A."@en . . "0"^^ . "2013-10-31+01:00"^^ . "mucopolysaccharidosis type III; lysosomal acetyltransferase; cell biology of lysosomes"@en . "3"^^ . "0"^^ . "3"^^ . . "Acetyl-coenzyme A:glucosaminide N-acetyltransferase (HGSNAT) catalyses lysosomal degradation of glycosaminoglycan heparan sulfate. The inherited deficiency of HGSNAT results in its lysosomal storage and in clinical phenotype of MPSIIIC. Biochemical and proteomic approaches will be employed to characterize partner molecules of HGSNAT (lipids and proteins), which can participate in the normal enzymatic function of HGSNAT, but also in higher ordering of lysosomal membranes. Cellular context of HGSNAT will be evaluated both in terms of organellar distribution, lysosomal targeting and sub-compartmentalization of lysosomal membranes as well as by defining HGSNAT molecular partners (substrate or other lysosomal proteins). The aim of the project is the detailed characterization of the properties, molecular partners and intracellular transport of HGSNAT. Strategy for targeting of HGSNAT to the lysosomal compartment could thus be proposed for therapeutic applications."@en . "1"^^ . . .