The crystal structure of the Michaelis complex between the Fab fragment of
ferrochelatase antibody 7G12 and its substrate mesoporphyrin has been solved to
2.6-A resolution. The antibody-bound mesoporphyrin clearly adopts a nonplanar
conformation and reveals that the antibody catalyzes the porphyrin metallation
reaction by straining/distorting the bound substrate toward the transition-state
configuration. The crystal structures of the Fab fragment of the germ-line
precursor antibody to 7G12 and its complex with the hapten N-methylmesoporphyrin
have also been solved. A comparison of these structures with the corresponding
structures of the affinity-matured antibody 7G12 reveals the molecular mechanism
by which the immune system evolves binding energy to catalyze this reaction.
Figure 2.
Fig. 2. Out-of-plane displacement of the porphyrin ring
atoms from the porphyrin least-squares plane for MP (blue) and
NMP (pink) bound to antibody 7G12. The porphyrin atoms that are
involved in the same pyrrole ring are connected to give a
pentagon shape. A-D denote the porphyrin pyrroles as in Fig. 1C,
and N denotes the pyrrole nitrogen atoms of the porphyrin
molecule.
Figure 4.
Fig. 4. The difference in electrostatic surface potential
of the antibody-combining site in the germ-line and
affinity-matured Fab and the changes upon the binding of NMP and
MP. The red and blue colors correspond to negative and positive
surface potential, respectively. The figure was prepared with
GRASP (28).
