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Human mutation

A phosphoglycerate kinase mutant (PGK Herlev; D285V) in a Danish patient with isolated chronic hemolytic anemia: mechanism of mutation and structure-function relationships.


PMID 9744480

Abstract

Phosphoglycerate kinase (PGK) is a X-linked enzyme that plays a key role in the glycolytic pathway. Twelve different variants have already been reported. We describe a new PGK variant, PGK Herlev (Asp 285-->Val), in a 69-year-old Danish patient with isolated chronic hemolysis but who had no neurological or muscular disorders. The description of the mutation is based upon PCR amplification of specific regions of the PGK gene, followed by direct sequencing. Although observed in a male patient, this mutated X-linked gene is expressed partially, i.e., both normal and substituted nucleotides are present at the same position in a ratio of approximately 1:9. The most likely explanation for this observation is based on the occurrence of a somatic mutation of the PGK gene. The relationship of structure to function in PGK Herlev, as well as in all known variants, was examined by the use of a computer model based on the known spatial structure of the yeast and horse enzymes. Such an approach can be generalized to any other protein that has been crystallized and for which x-ray diffraction data are available in a species closely related to man.