Hemoglobin vancouver [α2β2 73(E17) Asp→ Tyr]: Its structure and function

Abstract

Hemoglobin Vancouver is a new abnormal hemoglobin with an amino acid substitution of the normal aspartyl residue 73 of the beta chain by a tyrosyl residue. It was discovered in a man of Chinese descent in association with beta thalassemia. It was subsequently detected in a sister in association with normal Hb A. The oxygen affinity of the abnormal hemoglobin is decreased but its subunit interaction is normal. The Bohr effect may be slightly increased. This is the fourth abnormal hemoglobin to be found with a substitution at beta73. The others are Hb C-Harlem (alpha2beta2 6Glu replaced by Val and 73 Asp replaced by Asn), Hb Korle-Bu (alpha2beta2 73Asp replaced by Asn), and Hb Mobile (alpha2beta2 73Asp replaced by Val). Although Hb Mobile was found in the present studies to have a decreased affinity for oxygen, Hbs C-Harlem and Korle-Bu have been reported to be normal. These observations of functional differences for variants of beta73 added to earlier observations of the role of the normal beta73 residue to the aggregation of sickle deoxyhemoglobin indicate that this position of the molecule may be important in intra as well as intermolecular interactions.