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1hba
From Proteopedia
(New page: 200px<br /> <applet load="1hba" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hba, resolution 2.1Å" /> '''HIGH-RESOLUTION X-RA...) |
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==Overview== | ==Overview== | ||
The mutation site in hemoglobin Rothschild (37 beta Trp----Arg) is located, in the "hinge region" of the alpha 1 beta 2 interface, a region that is, critical for normal hemoglobin function. The mutation results in greatly, reduced cooperativity and an oxygen affinity similar to that of hemoglobin, A [Gacon, G., Belkhodja, O., Wajcman, H., & Labie, D. (1977) FEBS Lett., 82, 243-246]. Crystal were grown under "low-salt" conditions [100 mM Cl-, in 10 mM phosphate buffer at pH 7.0 with poly(ethylene glycol) as a, precipitating agent]. The crystal structure of deoxyhemoglobin Rothschild, and the isomorphous crystal structure of deoxyhemoglobin A were refined at, resolutions of 2.0 and 1.9 A, respectively. The mutation-induced, structural changes were partitioned into components of (1) tetramer, rotation, (2) quaternary structure rearrangement, and (3) deformations of, tertiary structure. The quaternary change involves a 1 degree rotation of, the alpha subunit about the "switch region" of the alpha 1 beta 2, interface. The tertiary changes are confined to residues at the alpha 1, beta 2 interface, with the largest shifts (approximately 0.4 A) located, across the interface from the mutation site at the alpha subunit FG, corner-G helix boundary. Most surprising was the identification of a, mutation-generated anion-binding site in the alpha 1 beta 2 interface., Chloride binds at this site as a counterion for Arg 37 beta. The, requirement of a counterion implies that the solution properties of, hemoglobin Rothschild, in particular the dimer-tetramer equilibrium, should be very dependent upon the concentration and type of anions, present. | The mutation site in hemoglobin Rothschild (37 beta Trp----Arg) is located, in the "hinge region" of the alpha 1 beta 2 interface, a region that is, critical for normal hemoglobin function. The mutation results in greatly, reduced cooperativity and an oxygen affinity similar to that of hemoglobin, A [Gacon, G., Belkhodja, O., Wajcman, H., & Labie, D. (1977) FEBS Lett., 82, 243-246]. Crystal were grown under "low-salt" conditions [100 mM Cl-, in 10 mM phosphate buffer at pH 7.0 with poly(ethylene glycol) as a, precipitating agent]. The crystal structure of deoxyhemoglobin Rothschild, and the isomorphous crystal structure of deoxyhemoglobin A were refined at, resolutions of 2.0 and 1.9 A, respectively. The mutation-induced, structural changes were partitioned into components of (1) tetramer, rotation, (2) quaternary structure rearrangement, and (3) deformations of, tertiary structure. The quaternary change involves a 1 degree rotation of, the alpha subunit about the "switch region" of the alpha 1 beta 2, interface. The tertiary changes are confined to residues at the alpha 1, beta 2 interface, with the largest shifts (approximately 0.4 A) located, across the interface from the mutation site at the alpha subunit FG, corner-G helix boundary. Most surprising was the identification of a, mutation-generated anion-binding site in the alpha 1 beta 2 interface., Chloride binds at this site as a counterion for Arg 37 beta. The, requirement of a counterion implies that the solution properties of, hemoglobin Rothschild, in particular the dimer-tetramer equilibrium, should be very dependent upon the concentration and type of anions, present. | ||
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| + | ==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 17:15:15 2007'' |
Revision as of 15:08, 12 November 2007
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HIGH-RESOLUTION X-RAY STUDY OF DEOXYHEMOGLOBIN ROTHSCHILD 37BETA TRP-> ARG: A MUTATION THAT CREATES AN INTERSUBUNIT CHLORIDE-BINDING SITE
Contents |
Overview
The mutation site in hemoglobin Rothschild (37 beta Trp----Arg) is located, in the "hinge region" of the alpha 1 beta 2 interface, a region that is, critical for normal hemoglobin function. The mutation results in greatly, reduced cooperativity and an oxygen affinity similar to that of hemoglobin, A [Gacon, G., Belkhodja, O., Wajcman, H., & Labie, D. (1977) FEBS Lett., 82, 243-246]. Crystal were grown under "low-salt" conditions [100 mM Cl-, in 10 mM phosphate buffer at pH 7.0 with poly(ethylene glycol) as a, precipitating agent]. The crystal structure of deoxyhemoglobin Rothschild, and the isomorphous crystal structure of deoxyhemoglobin A were refined at, resolutions of 2.0 and 1.9 A, respectively. The mutation-induced, structural changes were partitioned into components of (1) tetramer, rotation, (2) quaternary structure rearrangement, and (3) deformations of, tertiary structure. The quaternary change involves a 1 degree rotation of, the alpha subunit about the "switch region" of the alpha 1 beta 2, interface. The tertiary changes are confined to residues at the alpha 1, beta 2 interface, with the largest shifts (approximately 0.4 A) located, across the interface from the mutation site at the alpha subunit FG, corner-G helix boundary. Most surprising was the identification of a, mutation-generated anion-binding site in the alpha 1 beta 2 interface., Chloride binds at this site as a counterion for Arg 37 beta. The, requirement of a counterion implies that the solution properties of, hemoglobin Rothschild, in particular the dimer-tetramer equilibrium, should be very dependent upon the concentration and type of anions, present.
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
1HBA is a Protein complex structure of sequences from Homo sapiens with CL and HEM as ligands. Full crystallographic information is available from OCA.
Reference
High-resolution X-ray study of deoxyhemoglobin Rothschild 37 beta Trp----Arg: a mutation that creates an intersubunit chloride-binding site., Kavanaugh JS, Rogers PH, Case DA, Arnone A, Biochemistry. 1992 Apr 28;31(16):4111-21. PMID:1567857
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