Mutants classes

Table 1 CFTR mutant classes and their molecular consequence...

One approach to calculating the stationary mutant distributions for longer sequences is to form classes of sequences within the quasi-species. These classes are defined by means of the Hamming distance between the master sequence and the sequence under consideration. Class 0 contains the master sequence exclusively, class 1 the v different one-error mutants, class 2 all v(v —1)/2 two-error mutants, and so on. In general we have all (JJ) fe-error mutants in class k. In order to be able to reduce the 2 -dimensional eigenvalue problem to dimension v 1, we make the assumption that all formation rate constants are equal within a given class. We write Aq for the master sequence in class 0, Ai for all one-error mutants in class 1, 4 2 for all two-error mutants in class 2, and in general A for all k error mutants in class k. 

Figure 17. Example of almost degenerate quasi-species. For system of binary sequences with chain length v = 50 relative stationary concentrations of 51 mutant classes (, ) are shown in region 0.972 > q> 0.952. Notice extremely sharp transition at = 0.9638 when new master sequence /iso, and its neighbors become dominant. At = 0.9546 usual error threshold observed. Selective values used in this example are A,o, = 10, 4,50, = 9.9,4,4,1 = 2, and all other 4,j = 1 for 1 = 1,. 48 cf. figure 5).

The Hamming distance d(i, k) of two sequences Ij and counts the number of digits in which they differ. The number of sequences in a mutant class, that is, the number of sequences with Hamming distance d 0,k) = d from a reference sequence Iq, is... 

In the case of penicillin G, the outward rotation about the C3-C4 bond can occur vithout conflict with protein side chains. It relaxes the strained conformation along this bond previously enforced by the four-membered ring. Moreover, this rotation improves hydrophobic contact of the dimethyl and the sulfur part of the thiazolidine ring of penicillin with two leucine side chains, thus offering an additional driving force for the outward rotation. Experimental evidence is provided by the observed rotation of 35.2° in this direction about the C3-C4 bond that occurs in the acyl-enzyme complex formed between benzyl penicillin and a mutant class A beta-lactamase (RTEM-1) blocked in deacylation [9]. 

Quantification of neplanocin A in the presence of aristeromycin was found to be such an example. Accurate quantification of neplanocin A under these circumstances was not possible using PLS regression performed on the whole data set (see Figure. 4) however, PCA followed by DFA was successfully used to discriminate between the mutant classes (Figure... 

Figure 5. Separation of S. citricolor mutant classes by DFA Twelve different strains were assigned to four classes on the basis of their antibiotic production 1) high aristeromycin 2) both aristeromycin and neplanocin A 3) high neplanocin A 4) low aristeromycin and low neplanocin A. (A) Using all 4 classes as input (B) using 3 classes as input after discrimination and removal of the class 1 cluster.

Fig. 3. Schematic diagrams of six capsulatus sphaeroides chim pi opoons generated by the chimera rescue technique described in the text "Mutant class" refers to the three classes of mutants identiried in the text "Chimera tested" refers to the identification number of the specific mutant The sqiproximate boundaries between capsulatus and sphaeroides sequences was determined by restriction msq ping.

Treatment of CBS deficiency includes a low-methionine diet, vitamin Bs, folic acid, and betaine (N-trimethylglycine) [1]. Betaine works by (re)methy-lating homocysteine to methionine, and it is used in conjunction with folic acid in the treatment of MTHFR deficiency [3]. Hydroxycobalamin should be given to patients with methylmalonic aciduria protein restriction, folic acid, vitamin Bg, betaine and other measures may also be appropriate, depending on which mutant class (cblA through cblG) a patient is assigned to by complementation analysis [3, 6]. 

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