Open AccessA missense mutation Pro157Arg in lipoprotein lipase (LPL Nijmegen ) resulting in loss of catalytic activity
Author(s) -
BRUIN Taco,
KASTELEIN John J. P.,
DIERMEN Denise E.,
MA Yuanhong,
HENDERSON Howard E.,
STUYT Paul M. J.,
STALENHOEF Anton F. H.,
STURK Augueste,
BRUNZELL John D.,
HAYDEN Michael R.
Publication year - 1992
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1992.tb17182.x
Subject(s) - missense mutation , mutant , lipoprotein lipase , microbiology and biotechnology , mutation , mutagenesis , biology , genetics , gene , site directed mutagenesis , biochemistry , enzyme
Here we report on the molecular defect that leads to a deficiency of lipoprotein lipase (LPL) activity in a proband of Dutch descent. Southern‐blot analysis of the LPL gene from the patient did not reveal any major DNA rearrangements. Sequencing of polymerase‐chain‐reaction‐amplified DNA revealed that the proband is a homozygote for G725C, resulting in a substitution of Pro157 for Arg. This substitution alters a restriction site for Pvu II, which allowed rapid identification of the mutant allele in family members. Site‐directed mutagenesis and transient expression of the mutant LPL in COS cells produced an enzymatically inactive protein, establishing the functional significance of this mutation. This naturally occurring mutation which alters the Pro157 adjacent to Asp156 of the proposed catalytic triad, indicates that this region of the protein is indeed crucial for LPL catalytic activity.