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| - | [[Image:1abw.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1abw| PDB=1abw | SCENE= }} | | {{STRUCTURE_1abw| PDB=1abw | SCENE= }} |
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| - | '''DEOXY RHB1.1 (RECOMBINANT HEMOGLOBIN)'''
| + | ===DEOXY RHB1.1 (RECOMBINANT HEMOGLOBIN)=== |
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| - | ==Overview==
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| - | BACKGROUND:. Potential blood substitutes can be based on hemoglobin. Two problems must be overcome with acellular hemoglobin-based blood substitutes, however: the oxygen affinity of purified human hemoglobin is too high for it to deliver oxygen to tissues, and hemoglobin tetramers dissociate into alphabeta dimers that can cause kidney damage. A modified form of hemoglobin, rHb 1.1, has reduced oxygen affinity as the result of an Asnbeta 108-->Lys mutation, and dimerization is prevented by the insertion of a glycine residue between the sequences of the normal alpha chains to produce one covalently continuous di-alpha-chain. Determination of the structure of rHb 1.1 would provide structure-based explanations for the altered properties of rHb 1.1. RESULTS:. We determined the structures of the deoxy form of rHb 1.1 at 2.0 resolution and of cyanomet-rHb 1.1 at 2.6 resolution. Deoxy-rHb 1.1 adopts the classic 'T state' quaternary structure, but cyanomet-rHb 1.1 adopts a novel quanternary structure, the B state. The most striking feature of the tertiary structures is a charged hydrogen bond involving Lysbeta 108 that is broken in the T-->B state transition. The glycine bridge within the di-alpha-chain is well defined in both structures and appears to cause adoption of the B state instead of the previously observed ligand-bound quaternary structures R or Y/R2. CONCLUSIONS:. A charged hydrogen bond between Lysbeta 108 and Tyrbeta35 is broken in the transition between the deoxy and ligand-bound forms of rHb 1.1. This structural change reduces the oxygen affinity of rHb 1.1 by changing the relative stability of deoxy and ligand-bound states. Furthermore, our observations highlight the importance of small conformational changes in allosteric proteins, even in their most rigid domains. Three ligand-bound quaternary structures of hemoglobin (R, Y/R2 and B) have now been described. In contrast, only one quaternary structure has been observed for deoxyhemoglobin (T). The structural degeneracy of the high oxygen affinity form of hemoglobin is an important reminder that allosteric proteins may have multiple quaternary structures that are functionally very similar. This degeneracy of quaternary structures has important implications for the regulation of allosteric proteins, because different quaternary structures may be stabilized by different allosteric effectors.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_9032082}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9032082 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_9032082}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Oxygen transport]] | | [[Category: Oxygen transport]] |
| | [[Category: Respiratory protein]] | | [[Category: Respiratory protein]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 30 13:50:46 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 16:33:06 2008'' |
Revision as of 13:33, 30 June 2008
Template:STRUCTURE 1abw
DEOXY RHB1.1 (RECOMBINANT HEMOGLOBIN)
Template:ABSTRACT PUBMED 9032082
About this Structure
1ABW is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structures of a hemoglobin-based blood substitute: insights into the function of allosteric proteins., Kroeger KS, Kundrot CE, Structure. 1997 Feb 15;5(2):227-37. PMID:9032082
Page seeded by OCA on Mon Jun 30 16:33:06 2008
