1cbm
From Proteopedia
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|PDB= 1cbm |SIZE=350|CAPTION= <scene name='initialview01'>1cbm</scene>, resolution 1.74Å | |PDB= 1cbm |SIZE=350|CAPTION= <scene name='initialview01'>1cbm</scene>, resolution 1.74Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CMO:CARBON+MONOXIDE'>CMO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1cbm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cbm OCA], [http://www.ebi.ac.uk/pdbsum/1cbm PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1cbm RCSB]</span> | ||
}} | }} | ||
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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: Arnone, A.]] | [[Category: Arnone, A.]] | ||
[[Category: Borgstahl, G E.O.]] | [[Category: Borgstahl, G E.O.]] | ||
| - | [[Category: CMO]] | ||
| - | [[Category: HEM]] | ||
| - | [[Category: SO4]] | ||
[[Category: oxygen transport]] | [[Category: oxygen transport]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:18:34 2008'' |
Revision as of 16:18, 30 March 2008
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| , resolution 1.74Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
THE 1.8 ANGSTROM STRUCTURE OF CARBONMONOXY-BETA4 HEMOGLOBIN: ANALYSIS OF A HOMOTETRAMER WITH THE R QUATERNARY STRUCTURE OF LIGANDED ALPHA2BETA2 HEMOGLOBIN
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.
About this Structure
1CBM is a Single protein structure of sequence from Homo sapiens. 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 Sun Mar 30 19:18:34 2008
