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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1996-10-9
|
| pubmed:abstractText |
Based on the properties of two low oxygen affinity mutated hemoglobins (Hb), we have engineered a double mutant Hb (rHb beta YD) in which the beta F41Y substitution is associated with K82D. Functional studies have shown that the Hb alpha 2 beta 2(C7)F41Y exhibits a decreased oxygen affinity relative to Hb A, without a significantly increased autooxidation rate. The oxygen affinity of the natural mutant beta K82D (Hb Providence-Asp) is decreased due to the replacement of two positive charges by two negative ones at the main DPG-binding site. The functional properties of both single mutants are interesting in the view of obtaining an Hb-based blood substitute, which requires: (1) cooperative oxygen binding with an overall affinity near 30 mm Hg at half saturation, at 37 degrees C, and in the absence of 2,3 diphosphoglycerate (DPG), and (2) a slow rate of autooxidation in order to limit metHb formation. It was expected that the two mutations were at a sufficient distance (20 A) that their respective effects could combine to form low oxygen affinity tetramers. The double mutant does display additive effects resulting in a fourfold decrease in oxygen affinity; it can insure, in the absence of DPG, an oxygen delivery to the tissues similar to that of a red cell suspension in vivo at 37 degrees C. Nevertheless, the rate of autooxidation, 3.5-fold larger than that of Hb A, remains a problem.
|
| pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/8771203-12172,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8771203-1363932,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8771203-1390701,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8771203-1390926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8771203-14343300,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8771203-1799407,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8771203-2306490,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8771203-3676434,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8771203-3935609,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8771203-4555506,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8771203-6330564,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8771203-8416284,
http://linkedlifedata.com/resource/pubmed/commentcorrection/8771203-8463233
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0961-8368
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
5
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
114-20
|
| pubmed:dateRevised |
2009-11-18
|
| pubmed:meshHeading | |
| pubmed:year |
1996
|
| pubmed:articleTitle |
Two mutations in recombinant Hb beta F41(C7)Y, K82 (EF6)D show additive effects in decreasing oxygen affinity.
|
| pubmed:affiliation |
INSERM U 299, Hôpital de Bicêtre, France.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|