title: Structural bases of Wolman disease and cholesteryl ester storage disease.
abstract: To elucidate the bases of Wolman disease (WD) and cholesteryl ester storage disease (CESD) from the viewpoint of enzyme structure, we constructed a structural model of human lysosomal acid lipase (LAL) using molecular modeling software Modeller. The results revealed that the residues responsible for WD/CESD tend to be less solvent-accessible than others. Then, we examined the structural changes in the LAL protein caused by the WD/CESD mutations, using molecular modeling software TINKER. The results indicated that conformational changes of the functionally important residues and/or large conformational changes tend to cause the severe clinical phenotype (WD), whereas small conformational changes tend to cause the mild clinical phenotype (CESD), although there have been several exceptions. Further structural analysis is required to clarify the relationship between the three-dimensional structural changes and clinical phenotypes.
authors.affiliation: Department of Medical Management and Informatics, Hokkaido Information University, Ebetsu, Hokkaido, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Saito
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ohno
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakuraba
mesh_terms: D015217:Cholesterol Ester Storage Disease / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D012984:Software; D002787:Sterol Esterase / Q000737:chemistry* / Q000235:genetics; D013329:Structure-Activity Relationship; D015223:Wolman Disease / Q000235:genetics* / Q000378:metabolism
chemical_list: D002787:Sterol Esterase