Structural analysis of clinically relevant pathogenic G6PD variants reveals the importance of tetramerization for G6PD activity.

ABSTRACT: Over 220 different amino acid variants have been identified in human glucose-6-phosphate dehydrogenase (G6PD), covering over 30% of the protein sequence. Many of these variants are pathogenic, causing varying degrees of G6PD deficiency with symptoms ranging from severe chronic anemia (class I) to milder triggered hemolytic episodes (classes II and III). The phenotypic effects of most G6PD variants have been reported, providing an opportunity to correlate phenotypic and structural information. In particular, we sought to investigate the tetramer interface of G6PD in relation to pathogenic variation, as there are conflicting reports indicating the importance of tetramerization for G6PD activity. Using a three-dimensional spatial scan statistic, hotspots of structural enrichment were identifi

SUBMITTER: Cunningham AD 

PROVIDER: S-EPMC6105287 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature