2dn1: Difference between revisions
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==Overview== | ==Overview== | ||
The most recent refinement of the crystallographic structure of, oxyhaemoglobin (oxyHb) was completed in 1983, and differences between this, real-space refined model and later R state models have been interpreted as, evidence of crystallisation artefacts, or numerous sub-states. We have, refined models of deoxy, oxy and carbonmonoxy Hb to 1.25 A resolution, each, and compare them with other Hb structures. It is shown that the, older structures reflect the software used in refinement, and many, differences with newer structures are unlikely to be physiologically, relevant. The improved accuracy of our models clarifies the disagreement, between NMR and X-ray studies of oxyHb, the NMR experiments suggesting a, hydrogen bond to exist between the distal histidine and oxygen ligand of, both the alpha and beta-subunits. The high-resolution crystal structure, also reveals a hydrogen bond in both subunit types, but with subtly, different geometry which may explain the very different behaviour when, this residue is mutated to glycine in alpha or beta globin. We also, propose a new set of relatively fixed residues to act as a frame of, reference; this set contains a similar number of atoms to the well-known, "BGH" frame yet shows a much smaller rmsd value between R and T state, models of HbA. | The most recent refinement of the crystallographic structure of, oxyhaemoglobin (oxyHb) was completed in 1983, and differences between this, real-space refined model and later R state models have been interpreted as, evidence of crystallisation artefacts, or numerous sub-states. We have, refined models of deoxy, oxy and carbonmonoxy Hb to 1.25 A resolution, each, and compare them with other Hb structures. It is shown that the, older structures reflect the software used in refinement, and many, differences with newer structures are unlikely to be physiologically, relevant. The improved accuracy of our models clarifies the disagreement, between NMR and X-ray studies of oxyHb, the NMR experiments suggesting a, hydrogen bond to exist between the distal histidine and oxygen ligand of, both the alpha and beta-subunits. The high-resolution crystal structure, also reveals a hydrogen bond in both subunit types, but with subtly, different geometry which may explain the very different behaviour when, this residue is mutated to glycine in alpha or beta globin. We also, propose a new set of relatively fixed residues to act as a frame of, reference; this set contains a similar number of atoms to the well-known, "BGH" frame yet shows a much smaller rmsd value between R and T state, models of HbA. | ||
==Disease== | |||
Known diseases associated with this structure: Erythremias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Erythremias, beta- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Erythrocytosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], HPFH, deletion type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Heinz body anemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Heinz body anemias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Heinz body anemias, beta- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Hemoglobin H disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Hypochromic microcytic anemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Methemoglobinemias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Methemoglobinemias, beta- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Sickle cell anemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Thalassemia, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Thalassemia-beta, dominant inclusion-body OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Thalassemias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Thalassemias, beta- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: oxygen transport]] | [[Category: oxygen transport]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:37:27 2007'' | ||
Revision as of 22:31, 12 November 2007
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1.25A resolution crystal structure of human hemoglobin in the oxy form
OverviewOverview
The most recent refinement of the crystallographic structure of, oxyhaemoglobin (oxyHb) was completed in 1983, and differences between this, real-space refined model and later R state models have been interpreted as, evidence of crystallisation artefacts, or numerous sub-states. We have, refined models of deoxy, oxy and carbonmonoxy Hb to 1.25 A resolution, each, and compare them with other Hb structures. It is shown that the, older structures reflect the software used in refinement, and many, differences with newer structures are unlikely to be physiologically, relevant. The improved accuracy of our models clarifies the disagreement, between NMR and X-ray studies of oxyHb, the NMR experiments suggesting a, hydrogen bond to exist between the distal histidine and oxygen ligand of, both the alpha and beta-subunits. The high-resolution crystal structure, also reveals a hydrogen bond in both subunit types, but with subtly, different geometry which may explain the very different behaviour when, this residue is mutated to glycine in alpha or beta globin. We also, propose a new set of relatively fixed residues to act as a frame of, reference; this set contains a similar number of atoms to the well-known, "BGH" frame yet shows a much smaller rmsd value between R and T state, models of HbA.
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
2DN1 is a Protein complex structure of sequences from Homo sapiens with HEM, OXY and MBN as ligands. This structure superseeds the now removed PDB entry 2DFO. Full crystallographic information is available from OCA.
ReferenceReference
1.25 A resolution crystal structures of human haemoglobin in the oxy, deoxy and carbonmonoxy forms., Park SY, Yokoyama T, Shibayama N, Shiro Y, Tame JR, J Mol Biol. 2006 Jul 14;360(3):690-701. Epub 2006 May 30. PMID:16765986
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