Biological Ligands for Metal Ions - Biological Inorganic Chemistry - page 78

FIGURE 4.9 Mechanism of porphyrin metallation. (a) Out-of-plane saddling deformation used to describe a nonplanar distortion of the
porphyrin macrocycle in which two opposite pyrrole rings with unprotonated nitrogen atoms (blue spheres) point upwards, and the other two
pyrrole rings with protonated nitrogen atoms (blue and white spheres) point downwards. (b) Steps in the reaction mechanism for incorporation
of the metal ion (red) into porphyrin (pyrrole rings, green; unprotonated pyrrole nitrogen atoms, blue; protonated pyrrole nitrogen atoms with
protons, yellow) include (i) deformation of the porphyrin ring; (ii) formation of the first metal e porphyrin bond, followed by other ligand-
exchange steps leading to formation of a 'sitting-atop' complex (in which two pyrrolenine nitrogen atoms coordinate to the metal ion and two
protons remain on the pyrrole nitrogen atoms); and (iii) sequential deprotonation of the two pyrrole nitrogen atoms coupled with formation of
the metallated porphyrin. (From Al-Karadaghi et al., 2006 . Copyright 2006, with permission from Elsevier.)

sequential deprotonation of the two pyrrole nitrogen atoms coupled with formation of the metallated porphyrin.
The saddling of the porphyrin is an out-of-plane deformation, which exposes both of the protons and the lone pairs
of the nitrogen atoms of the porphyrin molecule in an appropriate arrangement for metal insertion.
The structure of several ferrochelatases has been determined, and it is clear that the porphyrin rings B, C, and D
are held in a very tight grip by conserved amino acids, whereas the A ring is distorted. Two metal-ion-binding sites
have been identified, one located at the surface of the molecule, occupied by a fully hydrated Mg 2 þ ion, and the
other located in the porphyrin-binding cleft, close to the distorted porphyrin ring A, with its nitrogen pointing
towards His183 and Glu264 ( Fig. 4.10 ). It has been proposed that the metal ion on the outermost site, by ligand
exchange with a series of acidic residues arranged along the helical edge of a -helix, 7 would be shuttled to the

inner site, there to be exchanged with the pyrrole nitrogens, resulting in insertion of the metal ion into the

p

FIGURE 4.10 Porphyrin and metal-ion-binding sites in ferrochelatase. (a) Structure of B. subtilis ferrochelatase in complex with the
transition-state inhibitor N-methylmesoporphyrin (N-MeMP). (b) Interaction of N-MeMP with amino acids in the substrate-binding cleft of B.
subtilis ferrochelatase. (c) Two metal-binding sites in B. subtilis ferrochelatase. The two sites are shown with a Zn 2 þ ion (grey sphere) and
a fully hydrated Mg 2 þ ion (green sphere). (From Al-Karadaghi et al., 2006 . Copyright 2006, with permission from Elsevier.)

7. For more information concerning this unusual type of helix, see Chapter 377.