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Titolo:
Effect of mutations of N- and C-terminal charged residues on the activity of LCAT
Autore:
Peelman, F; Vanloo, B; Verschelde, JL; Labeur, C; Caster, H; Taveirne, J; Verhee, A; Duverger, N; Vandekerckhove, J; Tavernier, J; Rosseneu, M;
Indirizzi:
State Univ Ghent, Flanders Interuniv Inst Biotechnol, Fac Med, Lab Lipoprot Chem, B-9000 Ghent, Belgium State Univ Ghent Ghent Belgium B-9000 poprot Chem, B-9000 Ghent, Belgium State Univ Ghent, Flanders Interuniv Inst Biotechnol, Fac Med, Dept Biochem, B-9000 Ghent, Belgium State Univ Ghent Ghent Belgium B-9000 ept Biochem, B-9000 Ghent, Belgium Aventis, Cardiovasc Dept, F-94403 Vitry, France Aventis Vitry France F-94403 tis, Cardiovasc Dept, F-94403 Vitry, France
Titolo Testata:
JOURNAL OF LIPID RESEARCH
fascicolo: 4, volume: 42, anno: 2001,
pagine: 471 - 479
SICI:
0022-2275(200104)42:4<471:EOMONA>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
LECITHIN-CHOLESTEROL ACYLTRANSFERASE; HUMAN PANCREATIC LIPASE; FISH-EYE DISEASE; ACYL TRANSFERASE; INTERFACIAL RECOGNITION; SEQUENCE ALIGNMENTS; A-I; IDENTIFICATION; CONSERVATION; TRUNCATION;
Keywords:
enzyme; lipase; structure; ionic interactions; phospholipid; lipoproteins;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Peelman, F State Univ Ghent, Flanders Interuniv Inst Biotechnol, Fac Med, Lab Lipoprot Chem, B-9000 Ghent, Belgium State Univ Ghent Ghent Belgium B-9000 , B-9000 Ghent, Belgium
Citazione:
F. Peelman et al., "Effect of mutations of N- and C-terminal charged residues on the activity of LCAT", J LIPID RES, 42(4), 2001, pp. 471-479

Abstract

On the basis of structural homology calculations, we previously showed that lecithin:cholesterol acyltransferase (LCAT), like lipases, belongs to thealpha/beta hydrolase fold family. As there is higher sequence conservationin the N-terminal region of LCAT, we investigated the contribution of the N- and C-terminal conserved basic residues to the catalytic activity of this enzyme. Most basic, and some acidic residues, conserved among LCAT proteins from different species, were mutated in the N-terminal (residues 1-210) and C-terminal (residues 211-416) regions of LCAT Measurements of LCAT-specific activity on a monomeric substrate, on low density lipoprotein (LDL), and on reconstituted high density lipoprotein (rHDL) showed that mutations of N-terminal conserved basic residues affect LCAT activity more than those in the C-terminal region. This agrees with the highest conservation of the alpha/beta hydrolase fold and structural homology with pancreatic lipase observed for the N-terminal region, and with the location of most of the natural mutants reported for human LCAT. The structural homology between LCAT and pancreatic lipase further suggests that residues R80, R147, and D145 of LCAT might correspond to residues R37, K107, and D105 of pancreatic lipase,which form the salt bridges D105-K107 and D105-R37. Natural and engineeredmutations at residues R80, D145, and R147 of LCAT are accompanied by a substantial decrease or loss of activity, suggesting that salt bridges betweenthese residues might contribute to the structural stability of the enzyme.

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Documento generato il 29/03/20 alle ore 08:11:41