Figure 4

Comparison of the sizes of wt hAID/N51A mutant catalytic pockets with the sizes of modified and non-modified C. (a) Catalytic pockets of wt hAID and the N51A mutant. The size of each pocket was defined by the distances between the selected atoms that belong to four pairs of amino acid residues: N51 (A51 in the case of the mutant) and Y114 (red dashed line); N51 (A51) and P86 (green dashed line); N51 (A51) and C87 (blue dashed line); and Y114 and H56 (black dashed line). The value of each distance is indicated and expressed in Å as a mean value from the distances measured for all individual frames of the MD trajectories. The distances were determined between the following heavy atoms: ND2 atom of N51; CB atom of A51; CE2 atom of Y114; CB atom of P86, SG atom of C87, and CE1 atom of H56. (b) Front and side views of hAID catalytic pocket. The distance between N51 (A51) and P86, i.e., the distance determining the breadth of a heterocyclic ring that can enter the pocket, is marked by a green arrow. The distance that defines the height of the catalytic pocket (between Y114 and H56) is marked by a black arrow. The depth of the catalytic pocket is marked by an orange arrow. (c) Range of changes observed for each distance throughout MD trajectories. The maximal and minimal values of each distance (expressed in Å) are indicated next to the graph. The colors are the same as in panel a. (d) The breadths of the heterocyclic rings of modified and non-modified C (green arrows). The value of each breadth is expressed in Å and includes vdW radii. The distance between C1′ and C4 of the heterocyclic ring is constant for each of the substrates (marked by an orange arrow) and corresponds to the depth of the catalytic pockets. A side view of the substrates is also shown. Because of the rotation of the hydroxymethyl group, the ring of 5 hmC is not completely flat.