1abw
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(New page: 200px<br /> <applet load="1abw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1abw, resolution 2.0Å" /> '''DEOXY RHB1.1 (RECOMB...)
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Revision as of 10:50, 8 November 2007
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DEOXY RHB1.1 (RECOMBINANT HEMOGLOBIN)
Overview
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.
About this Structure
1ABW is a Protein complex structure of sequences from Homo sapiens with HEM as ligand. 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
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