The microbial degradation of the plant cell wall is an important biological process that is highly relevant to environmentally significant industries such as the bioenergy and biorefining sectors. A major component of the wall is glucuronoxylan, a beta-1,4-linked xylose polysaccharide that is decorated with alpha-linked glucuronic and/or methylglucuronic acid (GlcA/MeGlcA). Recently three members of a glycoside hydrolase family, GH115, were shown to hydrolyze MeGlcA side chains from the internal regions of xylan, an activity that has not previously been described. Here we show that a dominant member of the human microbiota, Bacteroides ovatus, contains a GH115 enzyme, BoAgu115A, which displays glucuronoxylan alpha-(4-O-methyl)-glucuronidase activity. The enzyme is significantly more active against substrates in which the xylose decorated with GlcA/MeGlcA is flanked by one or more xylose residues. The crystal structure of BoAgu115A revealed a four domain protein in which the active site, comprising a pocket that abuts a cleft like structure, is housed in the second domain that adopts a TIM barrel fold. The third domain, a five helical bundle, and the C-terminal beta-sandwich domain make inter-chain contacts leading to protein dimerization. Informed by the structure of the enzyme in complex with GlcA in its open ring form, in conjunction with mutagenesis studies, the potential substrate binding and catalytically significant amino acids were identified. Based on the catalytic importance of residues located on a highly flexible loop, and the steric restriction imposed by the C-terminal domain of protomer 1 at the opening of the substrate binding cleft in protomer 2 (and vice versa), the enzyme is required to undergo a substantial conformational change to form a productive Michaelis complex with glucuronoxylan.