Figure 3.

Crystal structures of DHPS and DOHH and their active sites. A, human DHPS homotetramer (PDB codes 1ROZ and 1RLZ) complex with NAD (41). The two active sites at the dimer interfaces are indicated by black diamonds. B, active site residues of DHPS critical for catalysis (Lys³²⁹ and His²⁸⁸) and binding of spermidine (Asp²⁴³, Asp³¹⁶, Glu³²³, and Trp³²⁷) (23, 42). C, crystal structure of DOHH peroxo–diiron intermediate (PBD code 4D4Z) (50) consisting of eight HEAT repeats (helical hairpins), diiron center (red), and critical active-site residues (black and blue). D, a diagram of DOHH (11) active site showing peroxo (orange)–diiron (red) center and the four conserved His-Glu motifs critical for catalysis. His⁵⁶, His⁸⁹, Glu⁹⁰, His²⁰⁷, His²⁴⁰, and Glu²⁴¹ (black) are required for the binding of iron (49), and Glu⁵⁷ and Glu²⁰⁸ (blue) are required for binding of the terminal amino group of deoxyhypusine side chain (blue) (53).