1gzx

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 4: Line 4:
==Overview==
==Overview==
-
The cooperative binding of oxygen by haemoglobin results from restraints, on ligand binding in the T state. The unfavourable interactions made by, the ligands at the haems destabilise the T state and favour the high, affinity R state. The T <==> R equilibrium leads, in the presence of a, ligand, to a rapid increase in the R state population and therefore, generates cooperative binding. There is now considerable understanding of, this phenomenon, but the interactions that reduce ligand affinity in the T, state have not yet been fully explored, owing to the difficulties in, preparing T state haemoglobin crystals in which all the subunits are, oxygenated. A protocol has been developed to oxygenate deoxy T state adult, human haemoglobin (HbA) crystals in air at 4 C at all four haems without, significant loss of crystalline order. The X-ray crystal structure, determined to 2.1 A spacing, shows significant changes in the alpha and, beta haem pockets as well as changes at the alpha(1)beta(2) interface in, the direction of the R quaternary structure. Most of the shifts and, deviations from deoxy T state HbA are similar to, but larger than, those, previously observed in the T state met and other partially liganded T, state forms. They provide clear evidence of haem-haem interaction in the T, state.
+
The cooperative binding of oxygen by haemoglobin results from restraints on ligand binding in the T state. The unfavourable interactions made by the ligands at the haems destabilise the T state and favour the high affinity R state. The T <==> R equilibrium leads, in the presence of a ligand, to a rapid increase in the R state population and therefore generates cooperative binding. There is now considerable understanding of this phenomenon, but the interactions that reduce ligand affinity in the T state have not yet been fully explored, owing to the difficulties in preparing T state haemoglobin crystals in which all the subunits are oxygenated. A protocol has been developed to oxygenate deoxy T state adult human haemoglobin (HbA) crystals in air at 4 C at all four haems without significant loss of crystalline order. The X-ray crystal structure, determined to 2.1 A spacing, shows significant changes in the alpha and beta haem pockets as well as changes at the alpha(1)beta(2) interface in the direction of the R quaternary structure. Most of the shifts and deviations from deoxy T state HbA are similar to, but larger than, those previously observed in the T state met and other partially liganded T state forms. They provide clear evidence of haem-haem interaction in the T state.
==Disease==
==Disease==
Line 28: Line 28:
[[Category: transport]]
[[Category: transport]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:44:34 2008''
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:55:50 2008''

Revision as of 10:55, 21 February 2008

Image:1gzx.gif

1gzx, resolution 2.1Å

Drag the structure with the mouse to rotate

OXY T STATE HAEMOGLOBIN: OXYGEN BOUND AT ALL FOUR HAEMS

Contents

Overview

The cooperative binding of oxygen by haemoglobin results from restraints on ligand binding in the T state. The unfavourable interactions made by the ligands at the haems destabilise the T state and favour the high affinity R state. The T <==> R equilibrium leads, in the presence of a ligand, to a rapid increase in the R state population and therefore generates cooperative binding. There is now considerable understanding of this phenomenon, but the interactions that reduce ligand affinity in the T state have not yet been fully explored, owing to the difficulties in preparing T state haemoglobin crystals in which all the subunits are oxygenated. A protocol has been developed to oxygenate deoxy T state adult human haemoglobin (HbA) crystals in air at 4 C at all four haems without significant loss of crystalline order. The X-ray crystal structure, determined to 2.1 A spacing, shows significant changes in the alpha and beta haem pockets as well as changes at the alpha(1)beta(2) interface in the direction of the R quaternary structure. Most of the shifts and deviations from deoxy T state HbA are similar to, but larger than, those previously observed in the T state met and other partially liganded T state forms. They provide clear evidence of haem-haem interaction in the T state.

Disease

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 Structure

1GZX is a Protein complex structure of sequences from Homo sapiens with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Crystal structure of T state haemoglobin with oxygen bound at all four haems., Paoli M, Liddington R, Tame J, Wilkinson A, Dodson G, J Mol Biol. 1996 Mar 8;256(4):775-92. PMID:8642597

Page seeded by OCA on Thu Feb 21 12:55:50 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1gzx"
Personal tools