1G9V: High Resolution Crystal Structure Of Deoxy Hemoglobin Complexed With A Potent Allosteric Effector

Citation:
Abstract
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.
PDB ID: 1G9VDownload
MMDB ID: 15189
PDB Deposition Date: 2000/11/28
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 1.85  Å
Source Organism:
Similar Structures:
Biological Unit for 1G9V: tetrameric; determined by author
Molecular Components in 1G9V
Label Count Molecule
Proteins (4 molecules)
2
Hemoglobin Alpha Chain(Gene symbol: HBA1)
Molecule annotation
2
Hemoglobin Beta Chain(Gene symbol: HBB)
Molecule annotation
Chemicals (8 molecules)
1
4
2
2
3
2
* Click molecule labels to explore molecular sequence information.

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