Hemoglobin Warsaw (Phe super( beta 42(CD1)) arrow right Val), an unstable variant with decreased oxygen affinity. Characterization of its synthesis, functional properties, and structure

In Hb Warsaw Val replaces the Phe normally present at the heme contact position beta 42 (CD1). This variant is unstable, and it readily undergoes methemoglobin formation. In DEAE-cellulose chromatography, the variant hemoglobin co-eluted with Hb A; a partially heme-depleted fraction of the variant,...

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Bibliographic Details
Published in:The Journal of biological chemistry 1990-01, Vol.265 (1), p.126-132
Main Authors: Honig, G R, Vida, L N, Rosenblum, B B, Perutz, M F, Fermi, G
Format: Article
Language:English
Subjects:
blood
oxygen
Online Access:Get full text
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Summary:In Hb Warsaw Val replaces the Phe normally present at the heme contact position beta 42 (CD1). This variant is unstable, and it readily undergoes methemoglobin formation. In DEAE-cellulose chromatography, the variant hemoglobin co-eluted with Hb A; a partially heme-depleted fraction of the variant, representing 5-6% of the total hemoglobin, eluted separately and in pure form. The heme replete form of Hb Warsaw exhibited decreased oxygen affinity with a normal Bohr effect and normal cooperativity and interaction with 2,3-diphosphoglycerate (DPG). Structural analysis of deoxyhemoglobin containing roughly equal proportions of normal and variant beta chains showed that the replacement leaves a cavity next to heme that is large enough to hold a water molecule, which may account for the instability of Hb Warsaw. The resulting increase in the tilt of the proximal histidine relative to the heme plane, coupled with a possible stretching of the Fe-N sub( epsilon ) bond may account for the low oxygen affinity.
ISSN:0021-9258