Close-up of novel, putative type I missense mutations identified in the current study. Atoms are color-coded (green indicates carbon; blue, nitrogen; red, oxygen; and yellow, sulfur), and the mutated residues are labeled yellow. With exception of Gly261 (E) and His2082 (K), only residues within 4 Å of the mutation are shown. Hydrogen bonds are indicated with dotted lines. Notice that most affected residues are fully buried in the protein core and engage in multiple interactions with surrounding residues. (Further explanation for each mutation is in “Type I mutations.”)