2hhe: Difference between revisions
New page: left|200px<br /> <applet load="2hhe" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hhe, resolution 2.2Å" /> '''OXYGEN AFFINITY MODU... |
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==Overview== | ==Overview== | ||
A mutant human hemoglobin, beta (V1M+H2 delta), has been constructed., Analysis of the oxygen binding curves obtained at pH 8.3, where the Bohr, effect is inoperative, indicates that this mutation results in an, additional stabilization of the T-state conformation by 0.9 kcal/mol. The, crystal structure of deoxy-beta (V1M+H2 delta) has been determined to, 2.2-A resolution and compared with the deoxy structure of human hemoglobin, at the same resolution. In human hemoglobin, a sulfate anion is anchored, to the beta-chains by a complex network of H-bonds and electrostatic, interactions with the amino terminus and Lys beta 82. In the mutant, hemoglobin, the shortening of the amino-terminal region of the A helix by, 1 residue results in the formation of an intrachain electrostatic, interaction between the amino-terminal amino and Asp beta 79. This, eliminates the sulfate binding site, and the sulfate is replaced by two, water molecules. At variance with human hemoglobin, the alkaline Bohr, effect for beta (V1M+H2 delta) is not sensitive to the presence of Cl-., This indicates that the sulfate binding site in human hemoglobin also, serves as a Cl- binding site, and that the amino-terminal Val beta 1 is, essential for oxygen-linked Cl- binding to hemoglobin as well as the, Cl(-)-dependent Bohr effect. Analysis of the oxygen binding curves, indicates that the oxygen-linked Cl- ions are released upon binding of the, first oxygen molecule. | A mutant human hemoglobin, beta (V1M+H2 delta), has been constructed., Analysis of the oxygen binding curves obtained at pH 8.3, where the Bohr, effect is inoperative, indicates that this mutation results in an, additional stabilization of the T-state conformation by 0.9 kcal/mol. The, crystal structure of deoxy-beta (V1M+H2 delta) has been determined to, 2.2-A resolution and compared with the deoxy structure of human hemoglobin, at the same resolution. In human hemoglobin, a sulfate anion is anchored, to the beta-chains by a complex network of H-bonds and electrostatic, interactions with the amino terminus and Lys beta 82. In the mutant, hemoglobin, the shortening of the amino-terminal region of the A helix by, 1 residue results in the formation of an intrachain electrostatic, interaction between the amino-terminal amino and Asp beta 79. This, eliminates the sulfate binding site, and the sulfate is replaced by two, water molecules. At variance with human hemoglobin, the alkaline Bohr, effect for beta (V1M+H2 delta) is not sensitive to the presence of Cl-., This indicates that the sulfate binding site in human hemoglobin also, serves as a Cl- binding site, and that the amino-terminal Val beta 1 is, essential for oxygen-linked Cl- binding to hemoglobin as well as the, Cl(-)-dependent Bohr effect. Analysis of the oxygen binding curves, indicates that the oxygen-linked Cl- ions are released upon binding of the, first oxygen molecule. | ||
==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]] | ||
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Revision as of 23:26, 12 November 2007
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OXYGEN AFFINITY MODULATION BY THE N-TERMINI OF THE BETA CHAINS IN HUMAN AND BOVINE HEMOGLOBIN
OverviewOverview
A mutant human hemoglobin, beta (V1M+H2 delta), has been constructed., Analysis of the oxygen binding curves obtained at pH 8.3, where the Bohr, effect is inoperative, indicates that this mutation results in an, additional stabilization of the T-state conformation by 0.9 kcal/mol. The, crystal structure of deoxy-beta (V1M+H2 delta) has been determined to, 2.2-A resolution and compared with the deoxy structure of human hemoglobin, at the same resolution. In human hemoglobin, a sulfate anion is anchored, to the beta-chains by a complex network of H-bonds and electrostatic, interactions with the amino terminus and Lys beta 82. In the mutant, hemoglobin, the shortening of the amino-terminal region of the A helix by, 1 residue results in the formation of an intrachain electrostatic, interaction between the amino-terminal amino and Asp beta 79. This, eliminates the sulfate binding site, and the sulfate is replaced by two, water molecules. At variance with human hemoglobin, the alkaline Bohr, effect for beta (V1M+H2 delta) is not sensitive to the presence of Cl-., This indicates that the sulfate binding site in human hemoglobin also, serves as a Cl- binding site, and that the amino-terminal Val beta 1 is, essential for oxygen-linked Cl- binding to hemoglobin as well as the, Cl(-)-dependent Bohr effect. Analysis of the oxygen binding curves, indicates that the oxygen-linked Cl- ions are released upon binding of the, first oxygen molecule.
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
2HHE is a Protein complex structure of sequences from Homo sapiens with HEM as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Chloride ion independence of the Bohr effect in a mutant human hemoglobin beta (V1M+H2deleted)., Fronticelli C, Pechik I, Brinigar WS, Kowalczyk J, Gilliland GL, J Biol Chem. 1994 Sep 30;269(39):23965-9. PMID:7929044
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