3lhb: Difference between revisions

BACKGROUND: The hemoglobins of the sea lamprey are unusual in that, cooperativity and sensitivity to pH arise from an equilibrium between a, high-affinity monomer and a low-affinity oligomer. Although the crystal, structure of the monomeric cyanide derivative has previously been, determined, the manner by which oligomerization acts to lower the oxygen, affinity and confer a strong Bohr effect has, until now, been speculative., RESULTS: We have determined the crystal structure of deoxygenated lamprey, hemoglobin V by molecular replacement to 2.7 A resolution, in a crystal, form with twelve protomers in the asymmetric unit. The subunits are, arranged as six essentially identical dimers, with a novel subunit, interface formed by the E helices and the AB corner using the standard, hemoglobin helical designations. In addition to nonpolar interactions, the, interface includes a striking cluster of four glutamate residues. The, proximity of the interface to ligand-binding sites implicates a direct, effect on ligand affinity. CONCLUSIONS: Comparison of the deoxy structure, with that of the cyanide derivative revealed conformational changes that, appear to be linked to the functional behavior. Oligomerization is coupled, with a movement of the first half of the E helix by up to 1.0 A towards, the heme, resulting in steric interference of ligand binding to the deoxy, structure. The Bohr effect seems to result from proton uptake by glutamate, residues as they are buried in the interface. Unlike human and mollusc, hemoglobins, in which modulation of function is due to primarily proximal, effects, regulation of oxygen affinity in lamprey hemoglobin V seems to, depend on changes at the distal (ligand-binding) side of the heme group.

3LHB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Petromyzon_marinus Petromyzon marinus] with HEM as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Sites: F10, F11, F12, FE1, FE2, FE3, FE4, FE5, FE6, FE7, FE8 and FE9. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=3LHB OCA].  

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