Structural Basis for Substrate Selectivity in Human Maltase-glucoamylase and Sucrase-isomaltase N-terminal Domains

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Apr 2

PMID 20356844

Citations 58

Authors

Lyann Sim

Carly Willemsma

Sankar Mohan

Hassan Y Naim

B Mario Pinto

David R Rose

Affiliations

Soon will be listed here.

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.

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