Glucose 6-phosphate dehydrogenase mutations causing enzyme deficiency in a model of the tertiary structure of the human enzyme.
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.
Naylor
C E
CE
Laboratory of Molecular Biophysics, University of Oxford, UK.
Rowland
P
P
Basak
A K
AK
Gover
S
S
Mason
P J
PJ
Bautista
J M
JM
Vulliamy
T J
TJ
Luzzatto
L
L
Adams
M J
MJ
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
D005954:Glucosephosphate Dehydrogenase