1g9v

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spinqualitylabelsall models PDB ID 1g9v Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 1.85Å
Ligands:	, and
Coordinates:	save as pdb, mmCIF, xml

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. 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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