Catalytically inactive lecithin: cholesterol acyltransferase (LCAT) caused by a Gly 30 to Ser mutation in a family with LCAT deficiency
| Autor: | Akira Honjo, Hiroshi Mabuchi, John J. Albers, Xiao Ping Yang, Ichiro Koizumi, Junji Koizumi, Akihiro Inazu, Kouji Kajinami, Santica M. Marcovina |
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| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: |
Male
Protein Conformation Lipoproteins Sterol O-acyltransferase Restriction Mapping QD415-436 Transfection Biochemistry Phosphatidylcholine-Sterol O-Acyltransferase chemistry.chemical_compound Consanguinity Endocrinology Japan Lecithin Cholesterol Acyltransferase Deficiency medicine Missense mutation Animals Humans Point Mutation Deoxyribonucleases Type II Site-Specific Lecithin cholesterol acyltransferase deficiency Chemistry Cholesterol Point mutation Reverse cholesterol transport Cell Biology medicine.disease Molecular biology Pedigree COS Cells Female lipids (amino acids peptides and proteins) Sterol binding Phosphatidylcholine—sterol O-acyltransferase Cholesterol Esters |
| Zdroj: | Journal of Lipid Research, Vol 38, Iss 3, Pp 585-591 (1997) |
| ISSN: | 0022-2275 |
| Popis: | Plasma lecithin:cholesterol acyltransferase (LCAT) plays an important role in early steps of reverse cholesterol transport, i.e., cholesterol efflux from peripheral tissues and cholesterol esterification in HDL. However, structural and functional relationships of LCAT have not been fully elucidated. We described a missense mutation of Gly 30-to-Ser in a patient with classical LCAT deficiency. The proband was homozygous for the mutation and had a very low level of HDL cholesterol (2 mg/dl), with a half of normal LCAT mass (2.75 micrograms/ml), but no detectable or very low LCAT activity in endogenous and exogenous substrate assays. Both his mother and sister were heterozygous for the mutation, and had slightly decreased levels of HDL cholesterol (34 and 36 mg/dl, respectively). Transient expression study using COS cells indicated that mutant cDNA produces similar amounts of media protein as compared to wild type, but no detectable LCAT activity. The missense mutation may result in a near-native conformation without large effects on cellular secretion but a catalytically defective protein. Thus, the N-terminal domain appears crucial for enzymatic activity, in addition to the catalytically active consensus sequence of Gly179 to Gly183 and a putative sterol binding domain of Glu154 to Lys173. |
| Databáze: | OpenAIRE |
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