Publication: Molecular modeling of D151Y and M391T mutations in the LDL receptor
Issued Date
2008-12-12
Resource Type
ISSN
10902104
0006291X
0006291X
Other identifier(s)
2-s2.0-55549129921
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Mahidol University
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SCOPUS
Bibliographic Citation
Biochemical and Biophysical Research Communications. Vol.377, No.2 (2008), 355-360
Suggested Citation
Nutjaree Jeenduang, Chamras Promptmas, Klai upsorn S Pongrapeeporn, Sureerut Porntadavity Molecular modeling of D151Y and M391T mutations in the LDL receptor. Biochemical and Biophysical Research Communications. Vol.377, No.2 (2008), 355-360. doi:10.1016/j.bbrc.2008.09.151 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/18798
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Title
Molecular modeling of D151Y and M391T mutations in the LDL receptor
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Abstract
The low-density lipoprotein receptor (LDLR) is a key regulator of cholesterol homeostasis, and defects in the function of LDLR result in familial hypercholesterolemia (FH). In the present study, we performed structural analyses of two novel LDLR mutations, D151Y and M391T. Both mutations occurred in conserved residues of LDLR. The D151Y mutation, in the ligand binding domain, caused an elimination of a hydrogen bond in the calcium binding site, higher solvent accessibility and a loss of negative charge in the Y151 residue. On the other hand, the M391T mutation, in the β-propeller of the epidermal growth factor (EGF) precursor homology domain, caused an additional hydrogen bond to form, higher solvent accessibility and a distortion of the β-strand. These data suggest that the irregular structures of the mutated LDLRs are likely to cause the functional defect that contributes to the pathology of FH. © 2008 Elsevier Inc. All rights reserved.