Fig. 7

Plot showing conformational differences in PAH ^E390G, PAH ^V245A, PAH ^D415N, PAH ^R408Q, PAH ^Y414C and PAH ^R241C. Outermost layer indicates reported SNVs (gray, not validated; red, non-synonymous; green, synonymous) from dbSNP. a. Conservation scores represented as a histogram (blue, ACT domain; green, catalytic domain). These values are generated as described in section 5 and are not related to MODICT score. b and c. Amino acid sequences with residues colored according to their property (positively charged, red triangle; negatively charged, blue triangle, non-polar, gray circle; polar, pink circle; aromatic ring, green hexagon). d. Iterative MODICT scores of individual residue pairs (algorithm, Eq. 1) resulting from comparison of mutations with residual enzyme activity less than 50 % (more severe) against mutations with residual activity greater than 50 % (less severe, Table 1). Each blue histogram bin designates the contribution of a residue pair to the overall MODICT score (Higher bars mean more contribution as well as more the adverse effect of that residue pair on structural stability). These histogram bins are generated by iterative MODICT algorithm and are colored according to conservation. Single residue pairs with high blue bars are much less significant than consecutive "blocks" of high blue bars. Scarcity of these blocks in topmost layer (label: all) points to the fact that different regions are affected in each mutation. PAH ^Y414C and PAH ^R241C are compared to less severe mutations individually (middle and bottom layers). Note the differences in regions that are affected the most in each mutation. e. Important regions, SNVs and Indels are marked with boxes