No description available.

No description available.

The structure of protein is essentially important for life activities. Proteins can perform their functions only by specific structures. In this thesis, the kink and multi-kink model for protein description are reviewed. It is shown that most of the loop parts in Protein Databank (PDB) can be described by very limited number of kinks within the experimental precision. Furthermore, by applying the model into two well studied real proteins (myoglobin and villin headpiece HP35), it is shown that the multi-kink model gives correct folding pathway and thermal dynamical properties compared with the experimental results for both proteins. In particular, the kink model is computationally inexpensive compared with other existing models. In the last chapter, a new visualization method for the heavy atoms in the side-chain is presented.

Ceramide glucosyltransferase (CGT) is a key enzyme in glycosphingolipid (GSL) biosynthesis in eukaryotic cells. Inhibition of enzyme activity by an N-alkylated imino sugar, N-butyl-deoxynojirimycin (NB-DNJ), has been evaluated for the therapeutic treatment of inherited glycosphingolipid lysosomal storage diseases. To develop more selective drugs for potential clinical use, further investigation of possible side effects and the design of a more selective inhibitor is required. One concern for clinical use of NB-DNJ is the potential activation of CGT in vivo. When rats were treated with various concentrations of NB-DNJ for 13 weeks to assess the depletion of glycosphingolipids and up-regulation of CGT activity, the reduction of ganglioside levels was observed following an increase in NB-DNJ dose level up to 180 mg/kg/day. However, CGT activity levels were not significantly affected by NB-DNJ treatment. The lack of CGT up-regulation while reducing GSLs by NB-DNJ would be desirable in the clinic to avoid a rapid accumulation of GSLs if patient treatment was concluded. To aid in design of highly selective inhibitors for CGT, enzyme kinetic studies were performed using recombinant human CGT and five different imino sugars. The recombinant enzyme showed similar enzyme kinetics to a native enzyme from HL-60 cells. All the tested imino sugars showed a mixed-type inhibition for ceramide, and an increase in N-alkyl chain provided an improved uncompetitive inhibition. These data suggest that CGT may have two different sites for binding of imino sugars, and the N-alkyl chain length may affect the preference for binding site. When the protein sequence of CGT was analysed using www server programs to predict protein structure, a Rossman fold was predicted in the nucleotide-binding domain as observed in other nucleotide-sugar glycosyltransferase structures. Also, a significant folding similarity to bacterial glycosyltransferase SpsA was predicted. Based on these observations, a possible inhibitor-binding mechanism is discussed that may aid the design of highly selective inhibitors for CGT.

Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.

Thesis (D.Eng.)--University of Delaware, 2006. / Principal faculty advisor: Anne Skaja Robinson, Dept. of Chemical Engineering. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2008.

Thesis (Ph.D.) --University of Montana, 2009. / Title from author supplied metadata. Description based on contents viewed on June 11, 2009. ETD number: etd-03252009-151239. Author supplied keywords: Protein Folding ; Denatured State ; Random Coil ; Aggregation ; TR-FRET. Includes bibliographical references.

Thesis (Ph. D.)--University of Texas at Austin, 2002. / Vita. Includes bibliographical references. Available also from UMI Company.