Title

Crystalline ligand transitions in lamprey hemoglobin. Structural evidence for the regulation of oxygen affinity

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Date

5-8-2001

Document Type

Article

Subjects

Animals; Crystallization; Hemoglobins; Lampreys; Ligands; Oxygen; Protein Conformation

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The hemoglobins of the Sea Lamprey (Petromyzon marinus) exist in an equilibrium between low affinity oligomers, stabilized by proton binding, and higher affinity monomers, stabilized by oxygen binding. Recent crystallographic analysis revealed that dimerization is coupled with key changes at the ligand binding site with the distal histidine sterically restricting ligand binding in the deoxy dimer but with no significant structural rearrangements on the proximal side. These structural insights led to the hypothesis that oxygen affinity of lamprey hemoglobin is distally regulated. Here we present the 2.9-A crystal structure of deoxygenated lamprey hemoglobin in an orthorhombic crystal form along with the structure of these crystals exposed to carbon monoxide. The hexameric assemblage in this crystal form is very similar to those observed in the previous deoxy structure. Whereas the hydrogen bonding network and packing contacts formed in the dimeric interface of lamprey hemoglobin are largely unaffected by ligand binding, the binding of carbon monoxide induces the distal histidine to swing to positions that would preclude the formation of a stabilizing hydrogen bond with the bound ligand. These results suggest a dual role for the distal histidine and strongly support the hypothesis that ligand affinity in lamprey hemoglobin is distally regulated.

Rights and Permissions

Citation: J Biol Chem. 2001 Jul 13;276(28):26230-6. Epub 2001 May 4. Link to article on publisher's site

DOI of Published Version

10.1074/jbc.M101391200

Related Resources

Link to Article in PubMed

Journal Title

The Journal of biological chemistry

PubMed ID

11340069