Proteins individuality

Fig. 8.10 Titers of antibodies at day 50 induced by plant-derived CTB-2L21 recombinant protein. Balb/c mice were intraperitoneally immunized with leaf extract from CTB-2L21 transgenic plants. Animals were boosted at days 21 and 35. Each mouse received 20 pg of CTB-2L21 recombinant protein. Individual samples of mouse serum were titrated against 2L21 synthetic peptide,VP2 protein and a control peptide (amino acids 122-135 of hepatitis B virus surface antigen). Titers were expressed as the highest serum dilution to yield twice the absorbance mean of preimmune sera. M1-M6 mice 1 to 6 2L21 epitope from the VP2 protein of the canine parvovirus CTB cholera toxin B VP2 protein of the canine parvovirus that includes the 2L21 epitope.

Proteins Individual protein spedes and denatured forms... 

We have discussed both target receptors and pharmacokinetics in this book. Protein manufacture is under direct genetic control, and two factors are of particular relevance here. First, the precise structure and function of protein macromolecules (receptors) targeted by a specific drug molecule will vary in different individuals. Since the structure and function of the protein are directly related to how the drug molecule will interact with that protein, individuals responses to the drug will vary. Second, there are genetic variations in metabolic enzymes (proteins) and hence metabolism. Both of these processes fall neatly into the domain of pharmacoproteomics (see Section 14.8). 

Figure 9.31. y -Carhouic auhydrase. (Left) The zinc site of y-carbonic anhydrase. (Middle) The trimeric structure of the protein (individual chains are labeled A, B, and C). (Right) The protein is rotated to show a top-down view that highlights its threefold symmetry and the position of the zinc sites (green) at the interfaces between subunits. 

Constitutive Ras activation can also arise from a recessive loss-of-function mutation in a GTPase-acceleratlng protein (GAP). The normal GAP function is to accelerate hydrolysis of GTP and the conversion of active GTP-bound Ras to inactive GDP-bound Ras (see Figure 3-29). The loss of GAP leads to sustained Ras activation of downstream signal-transduction proteins. For example, neurofibromatosis, a benign tumor of the sheath cells that surround nerves, is caused by loss of both alleles of NFl, which encodes a GAP-type protein. Individuals with neurofibromatosis have inherited a single mutant NFl allele subsequent somatic mutation in the other allele leads to formation of neurofibromas. Thus NFl, like RB, is a tumor-suppressor gene, and neurofibromatosis, like hereditary retinoblastoma, is inherited as an autosomal dominant trait. 

In 1989 a group of scientists revealed the three-dimensional structure of the HIV protease. This structure is shown in the accompanying figure. This enzyme is necessary for viral replication because the virus has an unusual strategy for making all of its proteins. Rather than make each protein individually, it makes large "polyproteins" that must then be cut by the HIV protease to form the final proteins required for viral replication. 

Averse lor a large number of proteins. Individual proteins can diow large deviations from these values. 

Competitive Adsorption of Fibrinogen and Albumin. When a foreign surface contacts blood it encounters a complex mixture of plasma proteins. The adsorption rates and surface coverages determined for proteins individually will undoubtedly differ when several proteins challenge the surface simultaneously. Therefore, a study of the adsorption characteristics of multi-component protein solutions has been conducted using TIRF. When extrinsic labeling is employed, TIRF is particularly suitable for studying competitive adsorption. 

Specificity Single amino acid Local region of amino acids Global bop gene Individual colony or protein Individual H. salinarum ceU Protein or membrane patch... 

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