Mutational analysis

Before the elucidation of the CAR X-ray crystal structure, modeling studies mainly focused on the constitutive activity of the receptor. For example, homology modeling along with molecular dynamics simulations was combined to identify critical amino acid residues responsible for the constitutive activation [43]. Especially, the role of Tyr326 as a molecular mimicry of a bound ligand in the interaction with the AF-2 helix was underscored. Mutational analyses and the later elucidation of the human CAR X-ray crystal structure confirmed an important role of this amino acid for the receptor s constitutive activity [41,44]. 

Nishikawa, H., et al., Mass spectro-metric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCAl-BARDl ubiquitin ligase. / Biol Chem, 2004, 279(6), 3916-24. 

T2. Triggs-Raine, B., Richard, M., etal., Mutational analyses of Tay-Sachs disease Studies on Tay-Sachs carriers of French Canadian background living in New England. Am. J. Hum. Genet. 56(4), 870-879 (1995). 

A genetic screen for novel clock mutations in Drosophila sA to the discovery of the first kinase that plays a role in circadian rhythmicity (Price et al 1998). Doubletime dht) is a member of the casein kinase 1 (CKl) family, and is 86% identical to human casein kinase Is (CKls) within the kinase domain (Kloss et al 1998). Originally, two mutations were isolated that produce short (18 h dht ) and long (27 h dbt ) behavioural rhythms. Since then, many period-altering mutations and loss-of-function alleles have been described. The majority of these mutations reside in the kinase domain of dbt, altering its ability to bind and/or phosphorylate its substrate (Fig. 1). All of the DBT point mutations analysed alter the phosphorylation state and accumulation of PER, indicating that DBT affects... 

Table 3.7.2. shows the mean SD and (range) of plasma biotinidase activities as well as the activity ratio with 1.5 mM and 0.15 mM substrate obtained in our laboratory. The values in normal individuals (age 2 months to adult) are used as reference values, with the mean activity in the presence of 0.15 mM substrate used as the 100% value in calculations. These plasma samples were stored at - 20°C and assayed within 1 day to 2 months. Since mutation analyses were not performed, these controls may include individuals heterozygous for a mutation in the biotinidase gene. 

Who benefits from the analysis Mutation analyses in children should only be performed if there is an important medical consequence in childhood. In particular, carrier analyses in healthy siblings of children with metabolic disorders are not indicated and should not be carried out even when requested by the parents. 

Kobashi, N. Nishiyama, M. Tanokura, M. Kinetic and mutation analyses of aspartate kinase from Thermus flavus. J. Biosci. Bioeng., 87, 739-745 (1999)... 

W Sommergruber, J Seipelt, F Fessl, T Skern, HD Liebig, G Casari. Mutational analyses support a model for the HRV2 2A proteinase. Virology 234 203-214,1991. 

Wells JA (1991) Systematic mutational analyses of protein-protein interfaces, Methods Enzymol, 202 390-411... 

Zhao, Y, Thomas, C., Bremer, C., and Roy, P. (1994). Deletion and mutational analyses of bluetongue virus NS2 protein indicate that the amino but not the carboxy terminus of the protein is critical for RNA-protein interactions. J. Virol. 68, 2179-2185. 

Mutation analyses of the integrase gene have demonstrated that integration is essential for productive viral infection. Therefore, integration is among the... 

Mutational analyses of H region and promoter regions both revealed the existence of at least two essential DNA elements an O/E-like site and a homeodomain site (Vassalli et al. 2002 Rothman et al. 2005 Nishizumi et al. 2007). Mutations of these elements abolish the expression of OR genes in the transgenic systems. O/E proteins that bind to O/E-like sites and Lhx2 that binds to a homeodomain site are both required for OSN development (Wang et al. 2004 Hirota and Mombaerts 2004 Kolterud et al. 2004 Hirota et al. 2007). 

Mutational analyses showed that single amino acid mutations can greatly alter the activity of P-gp in a substrate-dependent manner (for review, see refs. 7,56). While amino acids whose mutation has a marked effect on substrate selectivity of P-gp are found in all the regions of the polypeptide, they cluster in TMs 5 and 6 of the N-terminal TMD and the corresponding TMs 11 and 12 of the C-terminal TMD of P-gp7, suggesting a role for these regions of the P-gp polypeptide in substrate recognition. 

Bjorheim J, Lystad S, Lindblom A, et al. Mutation analyses of KRAS exon 1 comparing three different techniques temporal temperature gradient electrophoresis, constant denaturant capillary electrophoresis and allele specific polymerase chain reaction. MutatRes. 1998 403 103-112. 

Yoshizawa K, Nagai H, Saktrrai S, et al. Clonality and K-ras mutation analyses of epithelia in intraductal papillary mucinous trrmor and mucinous cystic trrmor of the pancreas. Virchows Arch. 2002 441 437-443. 

Kennel SJ et al., Mutation analyses of a series of TNT-related compounds using the CHO-HPRT assay, J. Appl. Toxicol., 20, 441, 2000. 

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