Structure and function of normal and variant human phosphoglycerate kinase.

Abstract

Complete amino acid sequence of normal human phosphoglycerate kinase (PGK) was determined. The enzyme consists of 417 amino acid residues with acetylserine at the NH2-terminal and isoleucine at the COOH-terminal. The structural abnormality of PGK-II, which is fairly common in Southern Pacific populations, is a single amino acid substitution from threonine in the normal enzyme to asparagine in the variant enzyme at the 352nd position. The substitution induced no change in the enzyme activity, but induced strong binding of the variant enzyme with citrate. The structural abnormality of PGK-München is a single amino acid substitution from aspartic acid in the normal enzyme to asparagine in the variant enzyme at the 267th position. PGK-München is associated with red cell enzyme deficiency (about 20% of normal), and substantial heat instability. Therefore, the negative charge of an aspartyl residue at the 267th position must play a role in maintaining the stability of the enzyme molecule. Possible mechanisms of hemolysis due to hereditary deficiency of PGK are discussed.