Structural basis for substrate selectivity in human maltase-glucoamylase and sucrase-isomaltase N-terminal domains.
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Sim L, Willemsma C, Mohan S, Naim HY, Pinto BM, Rose DR
Structural basis for substrate selectivity in human maltase-glucoamylase and sucrase-isomaltase N-terminal domains.
J Biol Chem. 2010 Jun 4;285(23):17763-70. doi: 10.1074/jbc.M109.078980. Epub 2010 Mar 31.
- PubMed ID
- 20356844 [ View in PubMed]
- 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 (ntSI) has a broader specificity for both alpha-1,4- and alpha-1,6-oligosaccharides. Here we present the crystal structure of the human ntSI, 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 ntSI, including a narrow hydrophobic +1 subsite, which may account for its additional substrate specificity for alpha-1,6 substrates.