Direct observation of photolysis-induced tertiary structural changes in human haemoglobin; Crystal structure of alpha(Ni)-beta(Fe-CO) hemoglobin (laser unphotolysed)

File:1j40.gif


1j40, resolution 1.45Å

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OverviewOverview

Human Hb, an alpha2beta2 tetrameric oxygen transport protein that switches, from a T (tense) to an R (relaxed) quaternary structure during, oxygenation, has long served as a model for studying protein allostery in, general. Time-resolved spectroscopic measurements after photodissociation, of CO-liganded Hb have played a central role in exploring both protein, dynamical responses and molecular cooperativity, but the direct, visualization and the structural consequences of photodeligation have not, yet been reported. Here we present an x-ray study of structural changes, induced by photodissociation of half-liganded T-state and fully liganded, R-state human Hb at cryogenic temperatures (25-35 K). On photodissociation, of CO, structural changes involving the heme and the F-helix are more, marked in the alpha subunit than in the beta subunit, and more subtle in, the R state than in the T state. Photodeligation causes a significant, sliding motion of the T-state beta heme. Our results establish that the, structural basis of the low affinity of the T state is radically different, between the subunits, because of differences in the packing and chemical, tension at the hemes.

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

1J40 is a Protein complex structure of sequences from Homo sapiens with HNI, HEM, CMO and 2FU as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Direct observation of photolysis-induced tertiary structural changes in hemoglobin., Adachi S, Park SY, Tame JR, Shiro Y, Shibayama N, Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7039-44. Epub 2003 May 28. PMID:12773618

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