The picture of the results of AQUA-DUCT analysis were selected for recent cover of Bioinformatic issues! SEE MORE

COVER story: Cupin-type phosphoglucose isomerase (PfPGI) from the hyperthermophilic archaeon Pyrococcus furiosus catalyzes the reversible isomerization of glucose-6-phosphate to fructose-6-phosphate. Using a 3DM-based bioinformatics approach, a pair of amino acids in the periphery of the PfPGI structure was found to be the dominant co-evolving mutation. We designed a small smart library of variants to test their biochemical activity. Although the mutant structures and metal cofactor coordination were strikingly similar, variations in their activity were observed. Using the water tracking approach, we found that the subtle changes in the structure and dynamics of the amino acid side chains might have influenced regulation of solvent access in the vicinity of the catalytic Mn2+ ion and contributed to the mutants’ activity.