title: Promiscuity in ligand-binding: The three-dimensional structure of a Piromyces carbohydrate-binding module, CBM29-2, in complex with cello- and mannohexaose.
abstract: Carbohydrate-protein recognition is central to many biological processes. Enzymes that act on polysaccharide substrates frequently contain noncatalytic domains, "carbohydrate-binding modules" (CBMs), that target the enzyme to the appropriate substrate. CBMs that recognize specific plant structural polysaccharides are often able to accommodate both the variable backbone and the side-chain decorations of heterogeneous ligands. "CBM29" modules, derived from a noncatalytic component of the Piromyces equi cellulase/hemicellulase complex, provide an example of this selective yet flexible recognition. They discriminate strongly against some polysaccharides while remaining relatively promiscuous toward both beta-1,4-linked manno- and cello-oligosaccharides. This feature may reflect preferential, but flexible, targeting toward glucomannans in the plant cell wall. The three-dimensional structure of CBM29-2 and its complexes with cello- and mannohexaose reveal a beta-jelly-roll topology, with an extended binding groove on the concave surface. The orientation of the aromatic residues complements the conformation of the target sugar polymer while accommodation of both manno- and gluco-configured oligo- and polysaccharides is conferred by virtue of the plasticity of the direct interactions from their axial and equatorial 2-hydroxyls, respectively. Such flexible ligand recognition targets the anaerobic fungal complex to a range of different components in the plant cell wall and thus plays a pivotal role in the highly efficient degradation of this composite structure by the microbial eukaryote.
authors.affiliation: Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW, United Kingdom.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Charnock
authors.forename: David N
authors.initials: DN
authors.lastname: Bolam
authors.forename: Didier
authors.initials: D
authors.lastname: Nurizzo
authors.forename: Lóránd
authors.initials: L
authors.lastname: Szabó
authors.forename: Vincent A
authors.initials: VA
authors.lastname: McKie
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Gilbert
authors.forename: Gideon J
authors.initials: GJ
authors.lastname: Davies
mesh_terms: D001665:Binding Sites; D002240:Carbohydrate Sequence; D002241:Carbohydrates; D002480:Cellulase / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray / Q000379:methods; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics; D005690:Galactose / Q000031:analogs & derivatives; D006026:Glycoside Hydrolases / Q000737:chemistry / Q000235:genetics; D008024:Ligands; D008351:Mannans / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry*; D020089:Piromyces / Q000201:enzymology; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D002241:Carbohydrates; D005656:Fungal Proteins; D008024:Ligands; D008351:Mannans; C442224:NCP1 protein, Piromyces equi; D009844:Oligosaccharides; D011993:Recombinant Fusion Proteins; C012990:galactomannan; C099423:cellohexaose; C022901:(1-6)-alpha-glucomannan; C048068:mannopentaose; D006026:Glycoside Hydrolases; C023305:hemicellulase; D002480:Cellulase; D005690:Galactose