1g9v

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spinqualitylabelsall models 1g9v, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

HIGH RESOLUTION CRYSTAL STRUCTURE OF DEOXY HEMOGLOBIN COMPLEXED WITH A POTENT ALLOSTERIC EFFECTOR

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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 SO4, HEM and RQ3 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

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