Bacteroides thetaiotaomicron generates diverse α-mannosidase activities through subtle evolution of a distal substrate-binding motif

TY - JOUR

T1 - Bacteroides thetaiotaomicron generates diverse α-mannosidase activities through subtle evolution of a distal substrate-binding motif

AU - Thompson, Andrew J.

AU - Spears, Richard J.

AU - Zhu, Yanping

AU - Suits, Michael D.L.

AU - Williams, Spencer J.

AU - Gilbert, Harry J.

AU - Davies, Gideon J.

N1 - 2018, The Author(s).

PY - 2018/5/1

Y1 - 2018/5/1

N2 - A dominant human gut microbe, the well studied symbiont Bacteroides thetaiotaomicron (Bt), is a glyco-specialist that harbors a large repertoire of genes devoted to carbohydrate processing. Despite strong similarities among them, many of the encoded enzymes have evolved distinct substrate specificities, and through the clustering of cognate genes within operons termed polysaccharide-utilization loci (PULs) enable the fulfilment of complex biological roles. Structural analyses of two glycoside hydrolase family 92 α-mannosidases, BT3130 and BT3965, together with mechanistically relevant complexes at 1.8–2.5 Å resolution reveal conservation of the global enzyme fold and core catalytic apparatus despite different linkage specificities. Structure comparison shows that Bt differentiates the activity of these enzymes through evolution of a highly variable substrate-binding region immediately adjacent to the active site. These observations unveil a genetic/biochemical mechanism through which polysaccharide-processing bacteria can evolve new and specific biochemical activities from otherwise highly similar gene products.

AB - A dominant human gut microbe, the well studied symbiont Bacteroides thetaiotaomicron (Bt), is a glyco-specialist that harbors a large repertoire of genes devoted to carbohydrate processing. Despite strong similarities among them, many of the encoded enzymes have evolved distinct substrate specificities, and through the clustering of cognate genes within operons termed polysaccharide-utilization loci (PULs) enable the fulfilment of complex biological roles. Structural analyses of two glycoside hydrolase family 92 α-mannosidases, BT3130 and BT3965, together with mechanistically relevant complexes at 1.8–2.5 Å resolution reveal conservation of the global enzyme fold and core catalytic apparatus despite different linkage specificities. Structure comparison shows that Bt differentiates the activity of these enzymes through evolution of a highly variable substrate-binding region immediately adjacent to the active site. These observations unveil a genetic/biochemical mechanism through which polysaccharide-processing bacteria can evolve new and specific biochemical activities from otherwise highly similar gene products.

KW - Bacteroides thetaiotaomicron

KW - carbohydrates

KW - glycans

KW - glycoside hydrolase family 92

KW - substrate specificity

KW - α-mannosidase

UR - http://www.scopus.com/inward/record.url?scp=85046404579&partnerID=8YFLogxK

U2 - 10.1107/S2059798318002942

DO - 10.1107/S2059798318002942

M3 - Article

SN - 2059-7983

VL - 74

SP - 394

EP - 404

JO - Acta crystallographica. Section D, Structural biology

JF - Acta crystallographica. Section D, Structural biology

IS - 5

ER -