1j7y: Difference between revisions

==Overview==

The effect of mutagenesis on O(2), CO, and NO binding to mutants of human, hemoglobin, designed to modify some features of the reactivity that hinder, use of hemoglobin solutions as blood substitute, has been extensively, investigated. The kinetics may be interpreted in the framework of the, Monod-Wyman-Changeux two-state allosteric model, based on the, high-resolution crystallographic structures of the mutants and taking into, account the control of heme reactivity by the distal side mutations. The, mutations involve residues at topological position B10 and E7, i.e., Leu, (B10) to Tyr and His (E7) to Gln, on either the alpha chains alone, (yielding the hybrid tetramer Hbalpha(YQ)), the beta chains alone (hybrid, tetramer Hbbeta(YQ)), or both types of chains (Hb(YQ)). Our data indicate, that the two mutations affect ligand diffusion into the pocket, leading to, proteins with low affinity for O(2) and CO, and especially with reduced, reactivity toward NO, a difficult goal to achieve. The observed kinetic, heterogeneity between the alpha(YQ) and beta(YQ) chains in Hb(YQ) has been, rationalized on the basis of the three-dimensional structure of the active, site. Furthermore, we report for the first time an experiment of partial, CO binding, selective for the beta chains, to high salt crystals of the, mutant Hb(YQ) in the T-state; these crystallographic data may be, interpreted as "snapshots" of the initial events possibly occurring on, ligand binding to the T-allosteric state of this peculiar mutant Hb.

==About this Structure==

[[Category: globin]]