James E. Knapp, Reinhard Pahl, Jordi Cohen, Jeffry C. Nichols, Klaus Schulten,
Quentin H. Gibson, Vukica Srajer, and William E. Royer Jr.
Ligand migration and cavities within scapharca dimeric HbI: Studies
by time-resolved crystallography, Xe binding, and computational analysis.
Structure, 17:1494-1504, 2009.
(PMC: 2785043)
KNAP2009
As in many other hemoglobins, no direct route for migration of ligands between solvent and active site is evident from crystal structures of Scapharca inaequivalvis dimeric HbI. Xenon (Xe) and organic halide binding experiments along with computational analysis presented here reveal protein cavities as potential ligand migration routes. Time-resolved crystallographic experiments show that photodissociated carbon monoxide (CO) docks within 5ns at the distal pocket B-site and at more remote Xe4 and Xe2 cavities. CO rebinding is not affected by the presence of dichloroethane within the major Xe4 protein cavity, demonstrating that this cavity is not on the major exit/entrance pathway. The crystal lattice has a substantial influence on ligand migration, suggesting that significant conformational rearrangements may be required for ligand exit. Taken together, these results are consistent with a distal histidine gate as one important ligand entry and exit route, despite its participation in the dimeric interface.
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