1cbm
From Proteopedia
(New page: 200px<br /> <applet load="1cbm" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cbm, resolution 1.74Å" /> '''THE 1.8 ANGSTROM ST...) |
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==Overview== | ==Overview== | ||
The beta-chains isolated from the human hemoglobin alpha 2 beta 2, heterotetramer self-assemble to form a beta 4 homotetramer. We report the, structure of the carbonmonoxy-beta 4 (CO beta 4) tetramer refined at a, resolution of 1.8 A. Compared to the three known quaternary structures of, human hemoglobin, the T state, the R state and the R2 state, the, quaternary structure of CO beta 4 most closely resembles the R state., While the degree of structural similarity between CO beta 4 and the R, state of liganded alpha 2 beta 2 is quite high, differences between the, alpha and beta-chain sequences result in interesting alternative packing, arrangements at the subunit interfaces of CO beta 4. In particular, Arg40, beta and Asp99 beta interact across the CO beta 4 equivalent of the alpha, 1 beta 2 interface to form two symmetry-related salt bridges that have no, counterpart in either liganded or deoxyhemoglobin. Because these salt, bridges are near a 2-fold symmetry axis, steric constraints prevent their, simultaneous formation, and electron density images of Arg40 beta and, Asp99 beta show equally populated dual conformations for the side-chains, of both residues. Relative to the liganded alpha 2 beta 2 tetramer, the, Arg40 beta...Asp99 beta salt bridges introduce ionic interactions that, should strengthen the CO beta 4 tetramer. The CO beta 4 equivalent of the, alpha 1 alpha 2 and beta 1 beta 2 interfaces strengthens the tetramer, relative to the liganded alpha 2 beta 2 tetramer by tethering both ends of, the central cavity. (The entrance to the central cavity is altered so that, the N termini move closer together and the C termini further apart, forming an anion binding pocket that is absent in liganded alpha 2 beta 2, hemoglobin.) In contrast, analysis of the CO beta 4 counterpart of the, alpha 1 beta 1 interface indicates that this interface is weakened in the, CO beta 4 tetramer. These differences in interface stability provide a, structural explanation for the published observation that the alpha 2 beta, 2 tetramer assembles via a stable alpha 1 beta 1 dimer intermediate, whereas assembly of the CO beta 4 tetramer is characterized more, accurately by a monomer-tetramer equilibrium. | The beta-chains isolated from the human hemoglobin alpha 2 beta 2, heterotetramer self-assemble to form a beta 4 homotetramer. We report the, structure of the carbonmonoxy-beta 4 (CO beta 4) tetramer refined at a, resolution of 1.8 A. Compared to the three known quaternary structures of, human hemoglobin, the T state, the R state and the R2 state, the, quaternary structure of CO beta 4 most closely resembles the R state., While the degree of structural similarity between CO beta 4 and the R, state of liganded alpha 2 beta 2 is quite high, differences between the, alpha and beta-chain sequences result in interesting alternative packing, arrangements at the subunit interfaces of CO beta 4. In particular, Arg40, beta and Asp99 beta interact across the CO beta 4 equivalent of the alpha, 1 beta 2 interface to form two symmetry-related salt bridges that have no, counterpart in either liganded or deoxyhemoglobin. Because these salt, bridges are near a 2-fold symmetry axis, steric constraints prevent their, simultaneous formation, and electron density images of Arg40 beta and, Asp99 beta show equally populated dual conformations for the side-chains, of both residues. Relative to the liganded alpha 2 beta 2 tetramer, the, Arg40 beta...Asp99 beta salt bridges introduce ionic interactions that, should strengthen the CO beta 4 tetramer. The CO beta 4 equivalent of the, alpha 1 alpha 2 and beta 1 beta 2 interfaces strengthens the tetramer, relative to the liganded alpha 2 beta 2 tetramer by tethering both ends of, the central cavity. (The entrance to the central cavity is altered so that, the N termini move closer together and the C termini further apart, forming an anion binding pocket that is absent in liganded alpha 2 beta 2, hemoglobin.) In contrast, analysis of the CO beta 4 counterpart of the, alpha 1 beta 1 interface indicates that this interface is weakened in the, CO beta 4 tetramer. These differences in interface stability provide a, structural explanation for the published observation that the alpha 2 beta, 2 tetramer assembles via a stable alpha 1 beta 1 dimer intermediate, whereas assembly of the CO beta 4 tetramer is characterized more, accurately by a monomer-tetramer equilibrium. | ||
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Erythremias, beta- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], HPFH, deletion type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], Heinz body anemias, beta- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], 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-beta, dominant inclusion-body OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141900 141900]], 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 16:19:56 2007'' |
Revision as of 14:13, 12 November 2007
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THE 1.8 ANGSTROM STRUCTURE OF CARBONMONOXY-BETA4 HEMOGLOBIN: ANALYSIS OF A HOMOTETRAMER WITH THE R QUATERNARY STRUCTURE OF LIGANDED ALPHA2BETA2 HEMOGLOBIN
Contents |
Overview
The beta-chains isolated from the human hemoglobin alpha 2 beta 2, heterotetramer self-assemble to form a beta 4 homotetramer. We report the, structure of the carbonmonoxy-beta 4 (CO beta 4) tetramer refined at a, resolution of 1.8 A. Compared to the three known quaternary structures of, human hemoglobin, the T state, the R state and the R2 state, the, quaternary structure of CO beta 4 most closely resembles the R state., While the degree of structural similarity between CO beta 4 and the R, state of liganded alpha 2 beta 2 is quite high, differences between the, alpha and beta-chain sequences result in interesting alternative packing, arrangements at the subunit interfaces of CO beta 4. In particular, Arg40, beta and Asp99 beta interact across the CO beta 4 equivalent of the alpha, 1 beta 2 interface to form two symmetry-related salt bridges that have no, counterpart in either liganded or deoxyhemoglobin. Because these salt, bridges are near a 2-fold symmetry axis, steric constraints prevent their, simultaneous formation, and electron density images of Arg40 beta and, Asp99 beta show equally populated dual conformations for the side-chains, of both residues. Relative to the liganded alpha 2 beta 2 tetramer, the, Arg40 beta...Asp99 beta salt bridges introduce ionic interactions that, should strengthen the CO beta 4 tetramer. The CO beta 4 equivalent of the, alpha 1 alpha 2 and beta 1 beta 2 interfaces strengthens the tetramer, relative to the liganded alpha 2 beta 2 tetramer by tethering both ends of, the central cavity. (The entrance to the central cavity is altered so that, the N termini move closer together and the C termini further apart, forming an anion binding pocket that is absent in liganded alpha 2 beta 2, hemoglobin.) In contrast, analysis of the CO beta 4 counterpart of the, alpha 1 beta 1 interface indicates that this interface is weakened in the, CO beta 4 tetramer. These differences in interface stability provide a, structural explanation for the published observation that the alpha 2 beta, 2 tetramer assembles via a stable alpha 1 beta 1 dimer intermediate, whereas assembly of the CO beta 4 tetramer is characterized more, accurately by a monomer-tetramer equilibrium.
Disease
Known diseases associated with this structure: Erythremias, beta- OMIM:[141900], HPFH, deletion type OMIM:[141900], Heinz body anemias, beta- OMIM:[141900], Methemoglobinemias, beta- OMIM:[141900], Sickle cell anemia OMIM:[141900], Thalassemia-beta, dominant inclusion-body OMIM:[141900], Thalassemias, beta- OMIM:[141900]
About this Structure
1CBM is a Single protein structure of sequence from Homo sapiens with SO4, HEM and CMO as ligands. Full crystallographic information is available from OCA.
Reference
The 1.8 A structure of carbonmonoxy-beta 4 hemoglobin. Analysis of a homotetramer with the R quaternary structure of liganded alpha 2 beta 2 hemoglobin., Borgstahl GE, Rogers PH, Arnone A, J Mol Biol. 1994 Feb 25;236(3):817-30. PMID:8114096
Page seeded by OCA on Mon Nov 12 16:19:56 2007
Categories: Homo sapiens | Single protein | Arnone, A. | Borgstahl, G.E.O. | CMO | HEM | SO4 | Oxygen transport
