National Repository of Grey Literature 39 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Structural studies and tissue distribution of human GCPII and characterization of its rat and porcine orthologs
Rovenská, Miroslava ; Konvalinka, Jan (advisor) ; Jonák, Jiří (referee) ; Martásek, Pavel (referee)
Since GCPII is a potential pharmacological target, it is being extensively snrdied in many labs all around the world and these studies comprise many topics. This is minored also by this PhD thesis. The papers included here concem two major issues: 1. analysis ofGCPII structure and interactions with ligands; 2. study of CCPII distribution in tissues of human and two other species considered as potential animal models and kinetic characterization of the corresponding GCPII orthologs. Structural studies of GCPII active site and substrate binding are driven by the attempt to broaden the information that could help the rational design of novel small GCPII ligands, functioning either as inhibitors in neuronal damage or as imaging agents in cancer diagnosis. Two papers included in this thesis describe ligand binding in the GCPII active site in detail, with particular ernphasis on the Sl'pocket in one case and on the Sl pocket in the other' Based on our findings, we can describe a set of interactions goveming GCPII affinity to a substrate, accommodations that CCPII active site is capable of during ligand binding, the limits imposed on the ligand and tolerance of the enzyme to varying ligand nature. All these pieces of infomation are useful for the design of novel compounds with high affinity to GCPII' sufÍicient...
Molecular pathology of selected inherited hyperbilirubinemias
Šlachtová, Lenka ; Martásek, Pavel (advisor) ; Schneider, Bohdan (referee) ; Králová, Jarmila (referee)
Inherited hyperbilirubinemias are a group of metabolic disorders, characterized by increased levels of total serum bilirubin or its conjugated fraction. Most of these hyperbilirubinemias are inherited autosomal recessively and are manifested in young age. Increased bilirubin reflects the genetic disturbances in one of the enzymes of heme degradation pathway, the defect of bilirubin conjugation (UGT1A1 gene) or its transport (ABCC2, OATP1B1, OATP1B3). All of these proteins are involved not only in elimination of bilirubin, but various substrates; therefore the performed studies have a great pharmacogenomics impact. We have studied the molecular pathology of hereditary hyperbilirubinemias in Caucasian and Roma population and to compare the clinical and biochemical results with the molecular genetic data. We described the impact of compound defect of c.-3279T>G and g.175492_175493insTA on total serum bilirubin and calculated the linkage disequlibrium of these two variants in promoter region of UGT1A1 gene. We also verified, that the population distribution of both variants is in concordance with the literature. In our second study, we have described the rare conjugated hyperbilirubinemia Dubin-Johnson type among 7 Roma families. We have found a novel variant NG_011798.1:c.[1013_1014delTG] together with...
Molecular pathology of selected porphyria with skin manifestation
Sameh Anwar Hussein Farrag, Mohamed ; Martásek, Pavel (advisor) ; Baxová, Alice (referee) ; Raman, C. S. (referee)
Porphyria is a group of inherited metabolic disorders due to enzymatic defect of the heme biosynthesis resulting in the overproduction of the heme precursors' porphyrins in different body organs. The enzymes of the heme biosynthesis are encoded by corresponding genes in which any defect in any of these genes lead to a specific type of porphyria. Numerous mutations were detected in these genes leading to impairment in the enzyme function and therefore developing of the clinical manifestations of porphyria. The aim of the present work was to investigate the UROD gene in patients with porphyria cutanea tarda (PCT) and hepatoerythropoietic protoporphyria (HEP) as well as the FECH gene in patients with erythropoietic protoporphyria (EPP) on a molecular level. We identified numerous mutations in the FECH and the UROD genes in three different populations, Czech, Slovak, and Egyptian. We described the novel mutations in the UROD gene in HEP Arabic patients from Egypt as well in the FECH gene in patients with EPP of Czech and Slovak origin. We expressed mutatted UROD protein in prokaryotic system and found 19 % of the wild-type enzymatic activity. Moreover, the current study presents for the first time the frequency of the low expression allele IVS3-48c in the FECH gene in healthy controls from the Czech...

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