TY  - GEN
T1  - Modeling human glucose-6-phosphate dehydrogenase mutations using C. elegans GSPD-1
AU  - Loges, Luiza N.
AU  - Walstrom, Katherine M.
DO  - 10.17912/micropub.biology.000451
UR  - http://beta.micropublication.org/journals/biology/micropub-biology-000451/
AB  - Hundreds of different mutations in human glucose-6-phosphate dehydrogenase (G6PD) have been identified. Our goal was to test whether the C. elegans homolog, GSPD-1 (EC 1.1.1.49), was a good model for human G6PD mutants. The sequence of GSPD-1 (NP_502129) was aligned using BLASTP with human G6PD isoform b (NP_001035810.1) because this isoform encodes an active version of the protein (Altschul et al. 1990; Kanno et al. 1993). The sequences were 61% identical and 76% similar between amino acids 32-512 of G6PD and amino acids 34-520 of GSPD-1. We studied two mutations that in human G6PD were Asp58Asn in patients in Southern Italy and Arg246Leu in a patient in Tunisia (Vulliamy et al. 1988; Bendaoud et al. 2013). We chose these two mutants because they likely had residual enzyme activity, they had not been studied structurally before, and they were in residues that were conserved between the human and C. elegans orthologs. The protein sequence alignments between GSPD-1 and human G6PD in these two regions are shown in Figure 1A, and the corresponding mutations in GSPD-1 are D60N and R252L. The amino acids to the right of Asp60 are in an exterior loop, which may explain why these amino acids are less conserved than the surrounding amino acids, which are further inside the protein.
PY  - 2021
JO  - microPublication Biology
ER  -