title: Glucose 6-phosphate dehydrogenase mutations causing enzyme deficiency in a model of the tertiary structure of the human enzyme.
abstract: Human glucose 6-phosphate dehydrogenase (G6PD) has a particularly large number of variants resulting from point mutations; some 60 mutations have been sequenced to date. Many variants, some polymorphic, are associated with enzyme deficiency. Certain variants have severe clinical manifestations; for such variants, the mutant enzyme almost always displays a reduced thermal stability. A homology model of human G6PD has been built, based on the three-dimensional structure of the enzyme from Leuconostoc mesenteroides. The model has suggested structural reasons for the diminished enzyme stability and hence for deficiency. It has shown that a cluster of mutations in exon 10, resulting in severe clinical symptoms, occurs at or near the dimer interface of the enzyme, that the eight-residue deletion in the variant Nara is at a surface loop, and that the two mutations in the A- variant are close together in the three-dimensional structure.
authors.affiliation: Laboratory of Molecular Biophysics, University of Oxford, UK.
authors.forename: C E
authors.initials: CE
authors.lastname: Naylor
authors.forename: P
authors.initials: P
authors.lastname: Rowland
authors.forename: A K
authors.initials: AK
authors.lastname: Basak
authors.forename: S
authors.initials: S
authors.lastname: Gover
authors.forename: P J
authors.initials: PJ
authors.lastname: Mason
authors.forename: J M
authors.initials: JM
authors.lastname: Bautista
authors.forename: T J
authors.initials: TJ
authors.lastname: Vulliamy
authors.forename: L
authors.initials: L
authors.lastname: Luzzatto
authors.forename: M J
authors.initials: MJ
authors.lastname: Adams
mesh_terms: D000595:Amino Acid Sequence; D005954:Glucosephosphate Dehydrogenase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017354:Point Mutation; D011487:Protein Conformation
chemical_list: D005954:Glucosephosphate Dehydrogenase