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New page: left|200px<br /> <applet load="1bbb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bbb, resolution 1.7Å" /> '''A THIRD QUATERNARY S... |
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==Overview== | ==Overview== | ||
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. | 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. | ||
==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 16:07:58 2007'' | ||
Revision as of 17:01, 12 November 2007
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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 with HEM and CMO as ligands. 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
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