التفاصيل البيبلوغرافية
| العنوان: |
Relationship between structure and biochemical phenotype of lecithin:cholesterol acyltransferase (LCAT) mutants causing fish-eye disease |
| المؤلفون: |
Berlinda Vanloo, Frank Peelman, Kristof Deschuymere, Josee Taveirne, Annick Verhee, Catherine Gouyette, Christine Labeur, Joël Vandekerckhove, Jan Tavernier, Maryvonne Rosseneu |
| المصدر: |
Journal of Lipid Research, Vol 41, Iss 5, Pp 752-761 (2000) |
| بيانات النشر: |
Elsevier, 2000. |
| سنة النشر: |
2000 |
| المجموعة: |
LCC:Biochemistry |
| مصطلحات موضوعية: |
cholesterol, phospholipid, enzyme, lipase, HDL, LDL, Biochemistry, QD415-436 |
| الوصف: |
In order to test the hypothesis that fish-eye disease (FED) is due to a deficient activation of lecithin:cholesterol acyltransferase (LCAT) by its co-factor apolipoprotein (apo) A-I, we overexpressed the natural mutants T123I, N131D, N391S, and other engineered mutants in Cos-1 cells. Esterase activity was measured on a monomeric phospholipid enelogue, phospholipase A2 activity was measured on reconstituted high density lipoprotein (HDL), and acyltransferase activity was measured both on rHDL and on low density lipoprotein (LDL). The natural FED mutants have decreased phospholipase A2 activity on rHDL, which accounts for the decreased acyltransferase activity previously reported. All mutants engineered at positions 131 and 391 had decreased esterase activity on a monomeric substrate and decreased acyltransferase activity on LDL. In contrast, mutations at position 123 preserved these activities and specifically decreased phospholipase A2 and acyltransferase activites on rHDL. Mutations of hydrophilic residues in amphipathic helices α 3–4 and α His to an alanine did not affect the mutants' activity on rHDL. Based upon the 3D model built for human LCAT, we designed a new mutant F382A, which had a biochemical phenotype similar to the natural T123I FED mutant. These data suggest that residues T123 and F382, located N-terminal of helices α 3–4 and α His, contribute specifically to the interaction of LCAT with HDL and possibly with its co-factor apoA-I. Residues N131 and N391 seem critical for the optimal orientation of the two amphipathic helices necessary for the recognition of a lipoprotein substrate by the enzyme.—Vanloo, B., F. Peelman, K. Deschuymere, J. Taveirne, A. Verhee, C. Gouyette, C. Labeur, J. Vandekerckhove, J. Tavernier, and M. Rosseneu. Relationship between structure and biochemical phenotype of lecithin:cholesterol acyltransferase (LCAT) mutants causing fish-eye disease. J. Lipid Res. 2000. 41: 752–761. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
0022-2275 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S0022227520323841; https://doaj.org/toc/0022-2275 |
| DOI: |
10.1016/S0022-2275(20)32384-1 |
| URL الوصول: |
https://doaj.org/article/7a02b7b3a2b24f61956f4e17a5581ed8 |
| رقم الانضمام: |
edsdoj.7a02b7b3a2b24f61956f4e17a5581ed8 |
| قاعدة البيانات: |
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