PDBsum entry 1g9v

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protein ligands Protein-protein interface(s) links
Oxygen storage/transport PDB id
Protein chains
141 a.a. *
146 a.a. *
HEM ×4
RQ3 ×2
SO4 ×2
Waters ×260
* Residue conservation analysis
PDB id:
Name: Oxygen storage/transport
Title: High resolution crystal structure of deoxy hemoglobin complexed with a potent allosteric effector
Structure: Hemoglobin alpha chain. Chain: a, c. Hemoglobin beta chain. Chain: b, d
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: blood. Tissue: blood
Biol. unit: Tetramer (from PQS)
1.85Å     R-factor:   0.177     R-free:   0.208
Authors: M.K.Safo,C.M.Moure,J.C.Burnett,G.S.Joshi,D.J.Abraham
Key ref: M.K.Safo et al. (2001). High-resolution crystal structure of deoxy hemoglobin complexed with a potent allosteric effector. Protein Sci, 10, 951-957. PubMed id: 11316875
28-Nov-00     Release date:   06-Dec-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P69905  (HBA_HUMAN) -  Hemoglobin subunit alpha
142 a.a.
141 a.a.
Protein chains
Pfam   ArchSchema ?
P68871  (HBB_HUMAN) -  Hemoglobin subunit beta
147 a.a.
146 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   9 terms 
  Biological process     small molecule metabolic process   15 terms 
  Biochemical function     protein binding     9 terms  


Protein Sci 10:951-957 (2001)
PubMed id: 11316875  
High-resolution crystal structure of deoxy hemoglobin complexed with a potent allosteric effector.
M.K.Safo, C.M.Moure, J.C.Burnett, G.S.Joshi, D.J.Abraham.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21046405 A.Olianas, C.Meloni, I.Messana, M.T.Sanna, M.Castagnola, B.Manconi, S.Salvadori, B.Giardina, and M.Pellegrini (2011).
Striped mullet (Mugil cephalus) hemoglobin system: multiplicity and functional properties.
  J Comp Physiol B, 181, 187-197.  
16773073 B.Stea, E.Shaw, T.Pintér, J.Hackman, M.Craig, J.May, R.P.Steffen, and J.H.Suh (2006).
Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases.
  Br J Cancer, 94, 1777-1784.  
16613536 R.H.Engel, and V.G.Kaklamani (2006).
Role of efaproxiral in metastatic brain tumors.
  Expert Rev Anticancer Ther, 6, 477-485.  
15858266 L.N.Patskovska, Y.V.Patskovsky, S.C.Almo, and R.E.Hirsch (2005).
COHbC and COHbS crystallize in the R2 quaternary state at neutral pH in the presence of PEG 4000.
  Acta Crystallogr D Biol Crystallogr, 61, 566-573.
PDB codes: 1m9p 1nej
14574460 E.T.Donnelly, M.Kelley, and S.Rockwell (2004).
Effects of RSR13 and oxygen on the cytotoxicity of cisplatin and carboplatin to EMT6 mouse mammary tumor cells in vitro and in vivo.
  Cancer Chemother Pharmacol, 53, 43-50.  
16906231 S.M.Tschampel, and R.J.Woods (2003).
Quantifying the role of water in protein-carbohydrate interactions.
  J Phys Chem A, 107, 9175-9181.  
11914488 M.K.Safo, T.Boyiri, J.C.Burnett, R.Danso-Danquah, C.M.Moure, G.S.Joshi, and D.J.Abraham (2002).
X-ray crystallographic analyses of symmetrical allosteric effectors of hemoglobin: compounds designed to link primary and secondary binding sites.
  Acta Crystallogr D Biol Crystallogr, 58, 634-644.
PDB code: 1k0y
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