1qsh

File:1qsh.gif

spinqualitylabelsall models 1qsh, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

MAGNESIUM(II)-AND ZINC(II)-PROTOPORPHYRIN IX'S STABILIZE THE LOWEST OXYGEN AFFINITY STATE OF HUMAN HEMOGLOBIN EVEN MORE STRONGLY THAN DEOXYHEME

OverviewOverview

Studies of oxygen equilibrium properties of Mg(II)-Fe(II) and, Zn(II)-Fe(II) hybrid hemoglobins (i.e. alpha2(Fe)beta2(M) and, alpha2(M)beta2(Fe); M=Mg(II), Zn(II) (neither of these closed-shell metal, ions binds oxygen or carbon monoxide)) are reported along with the X-ray, crystal structures of alpha2(Fe)beta2(Mg) with and without CO bound. We, found that Mg(II)-Fe(II) hybrids resemble Zn(II)-Fe(II) hybrids very, closely in oxygen equilibrium properties. The Fe(II)-subunits in these, hybrids bind oxygen with very low affinities, and the effect of allosteric, effectors, such as proton and/or inositol hexaphosphate, is relatively, small. We also found a striking similarity in spectrophotometric, properties between Mg(II)-Fe(II) and Zn(II)-Fe(II) hybrids, particularly, the large spectral changes that occur specifically in the metal-containing, beta subunits upon the R-T transition of the hybrids. In crystals, both, alpha2(Fe)beta2(Mg) and alpha2(Fe-CO)beta2(Mg) adopt the quaternary, structure of deoxyhemoglobin. These results, combined with the, re-evaluation of the oxygen equilibrium properties of normal hemoglobin, low-affinity mutants, and metal substituted hybrids, point to a general, tendency of human hemoglobin that when the association equilibrium, constant of hemoglobin for the first binding oxygen molecule (K1), approaches 0.004 mmHg(-1), the cooperativity as well as the effect of, allosteric effectors is virtually abolished. This is indicative of the, existence of a distinct thermodynamic state which determines the lowest, oxygen affinity of human hemoglobin. Moreover, excellent agreement between, the reported oxygen affinity of deoxyhemoglobin in crystals and the lowest, affinity in solution leads us to propose that the classical T structure of, deoxyhemoglobin in the crystals represents the lowest affinity state in, solution.We also survey the oxygen equilibrium properties of various, metal-substituted hybrid hemoglobins studied over the past 20 years in our, laboratory. The bulk of these data are consistent with the Perutz's, trigger mechanism, in that the affinity of a metal hybrid is determined by, the ionic radius of the metal, and also by the steric effect of the distal, ligand, if present. However, there remains a fundamental contradiction, among the oxygen equilibrium properties of the beta substituted hybrid, hemoglobins.

DiseaseDisease

Known diseases associated with this structure: Erythremias, alpha- OMIM:[141800], Erythremias, beta- OMIM:[141900], Erythrocytosis OMIM:[141850], HPFH, deletion type OMIM:[141900], Heinz body anemia OMIM:[141850], Heinz body anemias, alpha- OMIM:[141800], Heinz body anemias, beta- OMIM:[141900], Hemoglobin H disease OMIM:[141850], Hypochromic microcytic anemia OMIM:[141850], Methemoglobinemias, alpha- OMIM:[141800], Methemoglobinemias, beta- OMIM:[141900], Sickle cell anemia OMIM:[141900], Thalassemia, alpha- OMIM:[141850], Thalassemia-beta, dominant inclusion-body OMIM:[141900], Thalassemias, alpha- OMIM:[141800], Thalassemias, beta- OMIM:[141900]

About this StructureAbout this Structure

1QSH is a Protein complex structure of sequences from Homo sapiens with HEM and HEG as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Magnesium(II) and zinc(II)-protoporphyrin IX's stabilize the lowest oxygen affinity state of human hemoglobin even more strongly than deoxyheme., Miyazaki G, Morimoto H, Yun KM, Park SY, Nakagawa A, Minagawa H, Shibayama N, J Mol Biol. 1999 Oct 8;292(5):1121-36. PMID:10512707

Page seeded by OCA on Mon Nov 12 18:56:16 2007