Title : Structural basis for substrate selectivity in human
maltase-glucoamylase and
sucrase-isomaltase N-terminal domains
Abstract :
- Human maltase-glucoamylase ( MGAM ) and sucrase-isomaltase ( SI ) are small intestinal enzymes that work concurrently to hydrolyze the mixture of linear alpha-1,4- and branched alpha-1,6-oligosaccharide substrates that typically make up terminal starch digestion products
- MGAM and SI are each composed of duplicated catalytic domains , N- and C-terminal, which display overlapping substrate specificities
- The N-terminal catalytic domain of human MGAM ( ntMGAM ) has a preference for short linear alpha-1,4-oligosaccharides , whereas N-terminal SI (nt SI ) has a broader specificity for both alpha-1,4- and alpha-1,6-oligosaccharides
- Here we present the crystal structure of the human nt SI , in apo form to 3.2 A and in complex with the inhibitor kotalanol to 2.15 A resolution
- Structural comparison with the previously solved structure of ntMGAM reveals key active site differences in nt SI , including a narrow hydrophobic +1 subsite , which may account for its additional substrate specificity for alpha-1,6 substrates