1G9V

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

Summary for 1G9V

• Entry DOI: 10.2210/pdb1g9v/pdb
• Descriptor: HEMOGLOBIN ALPHA CHAIN, HEMOGLOBIN BETA CHAIN, PROTOPORPHYRIN IX CONTAINING FE, ... (6 entities in total)
• Functional Keywords: hemoglobin tetramer, t state, allosteric, oxygen storage-transport complex, oxygen storage/transport
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 65421.98

Authors

Safo, M.K.,Moure, C.M.,Burnett, J.C.,Joshi, G.S.,Abraham, D.J. (deposition date: 2000-11-28, release date: 2000-12-06, Last modification date: 2023-08-09)

Primary citation

Safo, M.K.,Moure, C.M.,Burnett, J.C.,Joshi, G.S.,Abraham, D.J.
High-resolution crystal structure of deoxy hemoglobin complexed with a potent allosteric effector.
Protein Sci., 10:951-957, 2001

PubMed 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.

PubMed: 11316875
DOI: 10.1110/ps.50601

Experimental method

X-RAY DIFFRACTION (1.85 Å)