1g9v
From Proteopedia
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| - | [[Image:1g9v.gif|left|200px]]<br /> | + | [[Image:1g9v.gif|left|200px]]<br /><applet load="1g9v" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1g9v" size=" | + | |
caption="1g9v, resolution 1.85Å" /> | caption="1g9v, resolution 1.85Å" /> | ||
'''HIGH RESOLUTION CRYSTAL STRUCTURE OF DEOXY HEMOGLOBIN COMPLEXED WITH A POTENT ALLOSTERIC EFFECTOR'''<br /> | '''HIGH RESOLUTION CRYSTAL STRUCTURE OF DEOXY HEMOGLOBIN COMPLEXED WITH A POTENT ALLOSTERIC EFFECTOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of human deoxy hemoglobin (Hb) complexed with a | + | The crystal structure of human deoxy hemoglobin (Hb) complexed with a potent allosteric effector (2-[4-[[(3,5-dimethylanilino)carbonyl]methyl]phenoxy]-2-methylpropionic acid) = RSR-13) is reported at 1.85 A resolution. Analysis of the hemoglobin:effector complex indicates that two of these molecules bind to the central water cavity of deoxy Hb in a symmetrical fashion, and that each constrains the protein by engaging in hydrogen bonding and hydrophobic interactions with three of its four subunits. Interestingly, we also find that water-mediated interactions between the bound effectors and the protein make significant contributions to the overall binding. Physiologically, the interaction of RSR-13 with Hb results in increased oxygen delivery to peripheral tissues. Thus, this compound has potential therapeutic application in the treatment of hypoxia, ischemia, and trauma-related blood loss. Currently, RSR-13 is in phase III clinical trials as a radiosensitizing agent in the treatment of brain tumors. A detailed structural analysis of this compound complexed with deoxy Hb has important implications for the rational design of future analogs. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1G9V is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4, HEM and RQ3 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1G9V is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=HEM:'>HEM</scene> and <scene name='pdbligand=RQ3:'>RQ3</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G9V OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Abraham, D | + | [[Category: Abraham, D J.]] |
| - | [[Category: Burnett, J | + | [[Category: Burnett, J C.]] |
| - | [[Category: Joshi, G | + | [[Category: Joshi, G S.]] |
| - | [[Category: Moure, C | + | [[Category: Moure, C M.]] |
| - | [[Category: Safo, M | + | [[Category: Safo, M K.]] |
[[Category: HEM]] | [[Category: HEM]] | ||
[[Category: RQ3]] | [[Category: RQ3]] | ||
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[[Category: t state]] | [[Category: t state]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:47:50 2008'' |
Revision as of 10:47, 21 February 2008
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HIGH RESOLUTION CRYSTAL STRUCTURE OF DEOXY HEMOGLOBIN COMPLEXED WITH A POTENT ALLOSTERIC EFFECTOR
Contents |
Overview
The crystal structure of human deoxy hemoglobin (Hb) complexed with a potent allosteric effector (2-[4-[[(3,5-dimethylanilino)carbonyl]methyl]phenoxy]-2-methylpropionic acid) = RSR-13) is reported at 1.85 A resolution. Analysis of the hemoglobin:effector complex indicates that two of these molecules bind to the central water cavity of deoxy Hb in a symmetrical fashion, and that each constrains the protein by engaging in hydrogen bonding and hydrophobic interactions with three of its four subunits. Interestingly, we also find that water-mediated interactions between the bound effectors and the protein make significant contributions to the overall binding. Physiologically, the interaction of RSR-13 with Hb results in increased oxygen delivery to peripheral tissues. Thus, this compound has potential therapeutic application in the treatment of hypoxia, ischemia, and trauma-related blood loss. Currently, RSR-13 is in phase III clinical trials as a radiosensitizing agent in the treatment of brain tumors. A detailed structural analysis of this compound complexed with deoxy Hb has important implications for the rational design of future analogs.
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
1G9V is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
Reference
High-resolution crystal structure of deoxy hemoglobin complexed with a potent allosteric effector., Safo MK, Moure CM, Burnett JC, Joshi GS, Abraham DJ, Protein Sci. 2001 May;10(5):951-7. PMID:11316875
Page seeded by OCA on Thu Feb 21 12:47:50 2008
Categories: Homo sapiens | Protein complex | Abraham, D J. | Burnett, J C. | Joshi, G S. | Moure, C M. | Safo, M K. | HEM | RQ3 | SO4 | Allosteric | Hemoglobin tetramer | T state
