1bbb

File:1bbb.gif

spinqualitylabelsall models PDB ID 1bbb Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 1.7Å
Ligands:	and
Coordinates:	save as pdb, mmCIF, xml

A THIRD QUATERNARY STRUCTURE OF HUMAN HEMOGLOBIN A AT 1.7-ANGSTROMS RESOLUTION

OverviewOverview

Previous crystallographic studies have shown that human hemoglobin A can adopt two stable quaternary structures, one for deoxyhemoglobin (the T-state) and one for liganded hemoglobin (the R-state). In this paper we report our finding of a second quaternary structure (the R2-state) for liganded hemoglobin A. The magnitudes of the spatial differences between the R- and R2-states are as large as those between the R- and T-states. Of particular interest are the structural changes that occur as a result of R-T and R-R2 transitions at the so-called "switch" region of the critical alpha 1 beta 2 interface. In the R-state, His-97 beta 2 is positioned between Thr-38 alpha 1 and Thr-41 alpha 1, whereas in transition to the T-state His 97 beta 2 must "jump" a turn in the alpha 1 C helix to form nonpolar contacts with Thr-41 alpha 1 and Pro-44 alpha 1. This facet of the R-T transition presents a major steric barrier to the quaternary structure change. In the R2-state, His-97 beta 2 simply rotates away from threonines 38 alpha 1 and 41 alpha 1, breaking contact with these residues and allowing water access to the center of the alpha 1 beta 2 interface. With the switch region in an open position in the R2-state, His-97 beta 2 should be able to move by Thr-41 alpha 1 and make the transition to the T-state with a steric barrier that is less than that for the R-T transition. Thus the R2-state may function as a stable intermediate along a R-R2-T pathway. The T-, R-, and R2-states must coexist in solution. That is, the fact that these states can be crystallized implies that they are all energetically accessible structures. What remains to be determined are the T-to-R, T-to-R2, and R-to-R2 equilibrium constants for hemoglobin under various solution conditions and ligation states. Although this may prove to be difficult, we discuss previously published results which indicate that low concentrations of inorganic anions or low pH may favor the R2-state and at least one alpha 1 beta 2 interface mutation stabilizes a quaternary structure that is very similar to the R2-state.

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

1BBB is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

A third quaternary structure of human hemoglobin A at 1.7-A resolution., Silva MM, Rogers PH, Arnone A, J Biol Chem. 1992 Aug 25;267(24):17248-56. PMID:1512262

Page seeded by OCA on Thu Mar 20 10:08:43 2008