Site-mutation

Recently Alan Fersht, Cambridge University, has developed a protein engineering procedure for such studies. The technique is based on investigation of the effects on the energetics of folding of single-site mutations in a protein of known structure. For example, if minimal mutations such as Ala to Gly in the solvent-exposed face of an a helix, destabilize both an intermediate state and the native state, as well as the transition state between them, it is likely that the helix is already fully formed in the intermediate state. If on the other hand the mutations destabilize the native state but do not affect the energy of the intermediate or transition states at all, it is likely that the helix is not formed until after the transition state. 

DNA rerstriction site mutations and the radiation of Robinsonia (Asteraceae Senecioneae) on the Juan Fernandez Islands. Plant Syst. Evol. 184 233-239. 

Proline 195 was suggested by Gangola and Shamoo [210] as a component of the hypothetical Ca binding site. Mutation of Pro 195 to alanine and the mutation of several acidic residues in the same area [129] had no effect on the Ca transport, making this proposition also unlikely. 

GSH-S deficiency is a more frequent cause of GSH deficiency (HI7), and more than 20 families with this enzyme deficiency have been reported since the first report by Oort et al. (05). There are two distinct types of GSH-S deficiency with different clinical pictures. In the red blood cell type, the enzyme defect is limited to red blood cells and the only clinical presentation is mild hemolysis. In the generalized type, the deficiency is also found in tissues other than red blood cells, and the patients show not only chronic hemolytic anemia but also metabolic acidosis with marked 5-oxoprolinuria and neurologic manifestations including mental retardation. The precise mechanism of these two different phenotypes remains to be elucidated, because the existence of tissue-specific isozymes is not clear. Seven mutations at the GSH-S locus on six alleles—four missense mutations, two deletions, and one splice site mutation—have been identified (S14). 

K9. Kanno, H., Wei, D. C. C., Miwa, S., Chan, L. C., and Fujii, H., Identification of a 5 -splice site mutation and a missense mutation in homozygous pyruvate kinase deficiency cases found in Hong Kong. Blood 82 (Suppl. 1), 97a (1993). 

Hutton, M., Lendon, C. L., Rizzu, P. et al. Association of missense and 5 -splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393 702-705,1998. 

Shown are nonsense, missense, deletion/insertion and splice site mutations. The amino acid changes are predictions in most cases. 

Figure 3. Localisation of mutations in CBP and p300 in RTS patients (panel a) and tumour material (panel b). Indicated are nonsense, missense, deletion/insertion and splice site mutations, (c) Schematic representaion of the Rb-E2F and p53 pathways and the effects of CBP and p300 on these pathways...

Splice site mutation A1280-1305 Cell line Ovary Hetero (Ozdag et al, 2002)... 

Splice site mutation del1089-1095 Cell Une Lymphoid Hetero (Shigeno et al, 2004)... 

Splice-site mutations (choice E) occur at intron-exon boundaries and typically result in the loss of an exon or the inclusion of part of an intron in the coding sequence. Thus, more than a single amino acid -would he altered in a typical splice-site mutation. 

Sandhu SS, Ma TH, Peng Y, et al. 1989. Clastogenicity evaluation of seven chemicals commonly found at hazardous industrial waste sites. Mutat Res 224 437-445. 

These data emphasize the complex nature of the molecular mechanisms controlling polymorphic DPD activity in vivo. The clinical utility for genetic polymorphism testing to date is not optimal because of its low sensitivity and unknown specificity (28). Overall, it can be remarked that the splice site mutation IVS14+1G>A causes severe, even lethal, 5-FU-related toxicity. Unfortunately, the roles of other polymorphisms in the DPYD gene in the severe 5-FU-related toxicity are not clarified. 

Koch, T., Kroslak, T., Mayer, P., Raulf, E., and HoUt, V. (1997) Site mutation in the rat mu-opioid receptor demonstrates the involvement of calcium/calmodulin-dependent protein kinase II in agonist-mediated desensitization. J. Neurochem. 69, 1767-1770. 

Strasser-Wozak EM, Hattmannstorfer R, Hala M, et al. (1995) Splice site mutation in the glucocorticoid receptor gene causes resistance to glucocorticoid-induced apoptosis in a human acute leukemic cell line. Cancer Res. 55, 348-353. 

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