菅野　仁    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Professor (Fixed Term)
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Low substrate affinity of pyruvate kinase variant (PK Sapporo) caused by a single amino acid substitution (426 Arg-->Gln) associated with hereditary hemolytic anemia.
Journal	Formal name：Blood Abbreviation：Blood ISSN code：0006-4971(Print)0006-4971(Linking)
Volume, Issue, Page	81(9),pp.2439-41
Author and coauthor	Kanno H, Fujii H, Miwa S
Authorship	Lead author
Publication date	1993/05
Summary	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.
Document No.	8481523