Structural Basis for Substrate Selectivity in Human Maltase-Glucoamylase and Sucrase-Isomaltase N-terminal Domains
Structural Basis for Substrate Selectivity in Human Maltase-Glucoamylase and Sucrase-Isomaltase N-terminal Domains
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DOI：
10.1074/jbc.m109.078980
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发表时间：
2010-06-04
影响因子：
4.8
通讯作者：
Rose, David R.
中科院分区：
文献类型：
--
作者：
Sim, Lyann;Willemsma, Carly;Rose, David R.
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 angstrom and in complex with the inhibitor kotalanol to 2.15 angstrom 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.
