3LHB: The 2.7 Angstrom Crystal Structure Of Deoxygenated Hemoglobin From The Sea Lamprey (Petromyzon Marinus)

Citation:
Abstract
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.
PDB ID: 3LHBDownload
MMDB ID: 12226
PDB Deposition Date: 1999/1/12
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
Similar Structures:
Biological Unit for 3LHB: dimeric; determined by author
Molecular Components in 3LHB
Label Count Molecule
Proteins (2 molecules)
2
Protein (Hemoglobin)
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

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