1g9v
From Proteopedia
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|PDB= 1g9v |SIZE=350|CAPTION= <scene name='initialview01'>1g9v</scene>, resolution 1.85Å | |PDB= 1g9v |SIZE=350|CAPTION= <scene name='initialview01'>1g9v</scene>, resolution 1.85Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=RQ3:2-{4-[(3,5-DIMETHYLANILINO)-CARBONYL-METHYL]-PHENOXY}-2-METHYLPROPIONIC+ACID'>RQ3</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=1g9v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g9v OCA], [http://www.ebi.ac.uk/pdbsum/1g9v PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1g9v RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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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: Moure, C M.]] | [[Category: Moure, C M.]] | ||
[[Category: Safo, M K.]] | [[Category: Safo, M K.]] | ||
| - | [[Category: HEM]] | ||
| - | [[Category: RQ3]] | ||
| - | [[Category: SO4]] | ||
[[Category: allosteric]] | [[Category: allosteric]] | ||
[[Category: hemoglobin tetramer]] | [[Category: hemoglobin tetramer]] | ||
[[Category: t state]] | [[Category: t state]] | ||
| - | ''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 20:39:42 2008'' |
Revision as of 17:39, 30 March 2008
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| , resolution 1.85Å | |||||||
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| Ligands: | , , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HIGH RESOLUTION CRYSTAL STRUCTURE OF DEOXY HEMOGLOBIN COMPLEXED WITH A POTENT ALLOSTERIC EFFECTOR
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.
About this Structure
1G9V is a Protein complex structure of sequences from Homo sapiens. 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 Sun Mar 30 20:39:42 2008
