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Low substrate affinity of pyruvate kinase variant (PK Sapporo) caused by a
single amino acid substitution (426 Arg-->Gln) associated with
hereditary hemolytic anemia
H Kanno, H Fujii and S Miwa
Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
A point mutation (1277 CGG to CAG) was identified in the R-type pyruvate
kinase (PK) cDNA of a PK variant, PK Sapporo, associated with hereditary
non-spherocytic hemolytic anemia. The mutation causes a single amino acid
substitution from Arg to Gln at the 426th amino acid residue of human
R-type PK; consequently, the hydrophobicity around the mutated site is
drastically decreased. The amino acid change occurred in the eighth alpha
helix of A domain (A alpha 8) of PK, and it has been proposed that this
region as well as A alpha 7, A beta 7, and A beta 8 is a potassium (K+)
binding site. Because K+ binding to the PK subunit is considered to be
essential for substrate binding, the mutation might account for the
decreased affinity for phosphoenolpyruvate (PEP). This is compatible with
the fact that all the reported PK variants carrying point mutations in
those area have a high Michaelis constant (Km) for PEP.
Volume 81,
Issue 9,
pp. 2439-2441,
05/01/1993
Copyright © 1993 by The American Society of Hematology
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