Allosteric properties of haemoglobin beta 41 (C7) Phe-->Tyr: a stable, low-oxygen-affinity variant synthesized in Escherichia coli.
In human deoxy haemoglobin, the alpha 42(C7)Tyr-residue is hydrogen-bonded to beta 99(G1)Asp which stabilizes the low-oxygen-affinity deoxy conformation. We engineered a haemoglobin with Tyr for Phe at the homologous C7 position in beta-chains. The oxygen affinity of the variant is decreased about two-fold relative to Hb A while keeping similar KR and KT values. This mutant may be a candidate for the development of an artificial oxygen carrier, as it would not require an external effector for significant oxygen unloading in vivo.
Baudin
V
V
Institut National de la Santé et de la Recherche Médicale U299, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
Pagnier
J
J
Lacaze
N
N
Bihoreau
M T
MT
Kister
J
J
Marden
M
M
Kiger
L
L
Poyart
C
C
D000495:Allosteric Site; D001802:Blood Substitutes; D002248:Carbon Monoxide / Q000378:metabolism; D003001:Cloning, Molecular; D004926:Escherichia coli; D006454:Hemoglobins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010100:Oxygen / Q000378:metabolism*; D010649:Phenylalanine / Q000235:genetics; D013379:Substrate Specificity; D014443:Tyrosine / Q000235:genetics
D001802:Blood Substitutes; D006454:Hemoglobins; D014443:Tyrosine; D010649:Phenylalanine; D002248:Carbon Monoxide; C100003:deoxyhemoglobin; D010100:Oxygen