Architecturally complex <i>O</i> -glycopeptidases are customized for mucin recognition and hydrolysis
B. Pluvinage, Elizabeth Ficko‐Blean, Ilit Noach, C.P. Stuart, Nicole Thompson, Hayden McClure, Nakita Buenbrazo, Warren W. Wakarchuk, A.B. Boraston
Abstract
Significance Host-adapted bacteria, both pathogenic and commensal, have developed multimodular enzymatic systems to cope with the complex glycans found in the host environment, such as the highly competitive gut niche. Among these deployed enzymatic arsenals are O -glycopeptidases, which uniquely target proteins with O -linked glycan modification. Through meticulous structural and functional analyses, we probe the molecular basis of glycan recognition and illuminate the complete structure of an ultramultimodular O -glycopeptidase. This provides extraordinary insight into glycan recognition in the catalytic site of this unique class of peptidase. It also reveals how noncatalytic carbohydrate binding by ancillary modules and substrate recognition in the O -glycopeptidase active site can be specifically coordinated in three-dimensional space.