Browsing by Subject "Binding sites (Biochemistry)"
Now showing 1 - 8 of 8
Results Per Page
Sort Options
Item Biochemical studies of spermidine/spermine N¹-acetyltransferase, an important regulator of cellular polyamines(2008-08) Montemayor, Eric John, 1979-; Hoffman, David W., Ph. D.The polyamines spermine and spermidine play important roles in many cellular processes, and unusual levels of these polyamines have been associated with numerous human diseases. Spermidine/spermine N¹-acetyltransferase (SSAT) is an enzyme involved in polyamine regulation, where acetylation of polyamines by SSAT ultimately leads to their degradation or export from the cell. In this dissertation, x-ray crystallography and nuclear magnetic resonance (NMR) are used to provide insights into the structure and function of this important enzyme. X-ray crystallography provided two distinct views of SSAT: one of the enzyme in complex with coenzyme A (CoA), and another of the enzyme in complex with CoA and the polyamine spermine. Together, the two structures reveal structural plasticity in the active site of the enzyme. The complex with spermine provides a direct view of polyamine binding by SSAT, and shows that the enzyme relies heavily on associated water molecules to bind spermine; these water molecules also appear to form a "proton relay" between the primary amine of spermine and the side-chain of a conserved glutamate residue. Guided by the structural results, NMR methods were used to test hypotheses regarding the enzyme mechanism of SSAT. The activity of the enzyme over a range of solution conditions, and towards different polyamine substrates, was determined; the effects of mutating single amino acids in the enzyme were also evaluated. The enzyme appeared to be most active between pH 8.5 and 9.5, and mutation of the aforementioned glutamate significantly altered this behavior. This suggests the glutamate is directly involved in the acetyltransfer reaction, where it likely functions as a catalytic base though the proton relay in the enzyme active site. These studies advance our general understanding of how polyamines are regulated in mammalian cells, and have the potential to assist in developing new therapeutic options for human diseases involving polyamines.Item Item Isolation and characterization of DNA sequences bound by a class of nonhistone proteins(Texas Tech University, 1979-08) Jagodzinski, Linda L.All somatic cells of the same organism contain the same complement of genes. During cellular differentiation transcriptional specialization occurs. This process allows the selected expression of genetic information in specialized cells; e.g., only red blood cell precursors synthesize hemoglobin, only hepatocytes synthesize phenylalanine hydroxylase and serum albumin (159), and only estrogen induced oviduct cells synthesize ovalbumin. During differentiation certain genes function only at specific times and in particular tissues. Hence, portions of the eukaryotic genome must be prevented from expressing, in some manner, their genetic information. Evidence indicates that the chromosomal proteins participate in the regulation of gene activity. How this is accomplished and which components are involved are questions which are now being investigated.Item Molecular differences between the physiologically active (Pfr) and inactive (Pr) forms of phytochrome(Texas Tech University, 1983-05) Hahn, Tae-ryongNot availableItem Protein topography and binding properties of phytochrome(Texas Tech University, 1987-08) Choi, JungkapNot availableItem Sessler, Jonathan L. Pyrrole-based anion receptors : binding studies and progress towards attachment to solid support(2007-12) Barkey, Natalie Marie, 1980-; Sessler, Jonathan L.Anions have a wide range of importance both in chemical, as well as biological, systems; thus, the design and synthesis of novel receptors with the ability to selectively recognize or bind a specific class of anions is a rapidly developing field of supramolecular chemistry. A series of novel, acyclic pyrrole-based anion receptors will be presented. These systems, which are based on pyridine 2,6-dicarboxamides, bind nitrite and carboxylate anions with good selectivity in dichloroethane solution and are also capable of binding cyanide anions weakly. Control systems, incorporating a benzene-1,3-dicarboxamide spacer, or those wherein the connectivity of the amide linkage is "reversed," either failed to act as effective anion receptors or displayed very different selectivities. Such observations provide support for the notion that small perturbations in the structure of these receptors can lead to drastic changes in their anionbinding properties. Furthermore, efforts have been made to attach macrocyclic phosphate-binding receptors developed in the Sessler Group to cellulose solid supports. The idea is that these macrocycles, once bound to cellulose, will be capable of extracting phosphate from solutions. Studies on the macrocyclic loading level and extraction abilities of the receptors are underway, and will be presented herein.Item The Predator-Prey Interface Between Meria Coniospora and Panagrellus Redivivus(Texas Tech University, 1979-08) Tereletsky, Mark JosephNot Available.Item The retinol B [i.e. beta]-lactoglobulin complex(Texas Tech University, 1978-08) Fugate, Robert DanielNot available