In molecular biology, a carbohydrate-binding module (CBM) is a protein domain found in carbohydrate-active enzymes (for example glycoside hydrolases). The majority of these domains have carbohydrate-binding activity. Some of these domains are found on cellulosomalscaffoldin proteins. CBMs were previously known as cellulose-binding domains. CBMs are classified into numerous families, based on amino acid sequence similarity. There are currently (June 2011) 64 families of CBM in the CAZy database.
Carbohydrate-binding module family 2 (CBM2) contains two conserved cysteines - one at each extremity of the domain - which have been shown  to be involved in a disulfide bond. There are also four conserved tryptophans, two of which are involved in cellulose binding.
Carbohydrate-binding module family 4 (CBM4) includes the two cellulose-binding domains, CBD(N1) and CBD(N2), arranged in tandem at the N terminus of the 1,4-beta-glucanase, CenC, from Cellulomonas fimi. These homologous CBMs are distinct in their selectivity for binding amorphous and not crystalline cellulose. Multidimensional heteronuclear nuclear magnetic resonance (NMR) spectroscopy was used to determine the tertiary structure of the 152 amino acid N-terminal cellulose-binding domain from C. fimi 1,4-beta-glucanase CenC (CBDN1). The tertiary structure of CBDN1 is strikingly similar to that of the bacterial 1,3-1,4-beta-glucanases, as well as other sugar-binding proteins with jelly-roll folds. CBM4 and CBM9 are closely related.
Carbohydrate-binding module family 6 (CBM6) is unusual in that is contains two substrate-binding sites, cleft A and cleft B. Cellvibrio mixtus endoglucanase 5A contains two CBM6 domains, the CBM6 domain at the C-terminus displays distinct ligand binding specificities in each of the sustrate-binding clefts. Both cleft A and cleft B can bind cello-oligosaccharides, laminarin preferentially binds in cleft A, xylooligosaccharides only bind in cleft A and beta1,4,-beta1,3-mixed linked glucans only bind in cleft B.
Carbohydrate-binding module family 10 (CBM10) is found in two distinct sets of proteins with different functions. Those found in aerobic bacteria bind cellulose (or other carbohydrates); but in anaerobic fungi they are protein binding domains, referred to as dockerin domains. The dockerin domains are believed to be responsible for the assembly of a multiprotein cellulase/hemicellulase complex, similar to the cellulosome found in certain anaerobic bacteria.
In anaerobic bacteria that degrade plant cell walls, exemplified by Clostridium thermocellum, the dockerin domains of the catalyticpolypeptides can bind equally well to any cohesin from the same organism. More recently, anaerobic fungi, typified by Piromyces equi, have been suggested to also synthesise a cellulosome complex, although the dockerin sequences of the bacterial and fungalenzymes are completely different. For example, the fungal enzymes contain one, two or three copies of the dockerin sequence in tandem within the catalytic polypeptide. In contrast, all the C. thermocellum cellulosome catalytic components contain a single dockerin domain. The anaerobic bacterial dockerins are homologous to EF hands (calcium-binding motifs) and require calcium for activity whereas the fungal dockerin does not require calcium. Finally, the interaction between cohesin and dockerin appears to be species specific in bacteria, there is almost no species specificity of binding within fungal species and no identified sites that distinguish different species.
The of dockerin from P. equi contains two helical stretches and four short beta-strands which form an antiparallel sheet structure adjacent to an additional short twisted parallel strand. The N- and C-termini are adjacent to each other.
Carbohydrate-binding module family 11 (CBM11) is found in a number of bacterial cellulases. One example is the CBM11 of Clostridium thermocellum Cel26A-Cel5E, this domain has been shown to bind both β-1,4-glucan and β-1,3-1,4-mixed linked glucans. CBM11 has beta-sandwich structure with a concave side forming a substrate-binding cleft.
Carbohydrate-binding module family 12 (CBM12) comprises two beta-sheets, consisting of two and three antiparallel beta strands respectively. It binds chitin via the aromatic rings of tryptophan residues. CBM5 and CBM12 are distantly related.
Carbohydrate-binding module family 15 (CBM15), found in bacterial enzymes, has been shown to bind to xylan and xylooligosaccharides. It has a beta-jelly roll fold, with a groove on the concave surface of one of the beta-sheets.
Carbohydrate-binding module family 17 (CBM17) appears to have a very shallow binding cleft that may be more accessible to cellulose chains in non-crystalline cellulose than the deeper binding clefts of family 4 CBMs. Sequence and structural conservation in families CBM17 and CBM28 suggests that they have evolved through gene duplication and subsequent divergence. CBM17 does not compete with CBM28 modules when binding to non-crystalline cellulose. Different CBMs have been shown to bind to different sirtes in amorphous cellulose, CBM17 and CBM28 recognise distinct non-overlapping sites in amorphous cellulose.
Carbohydrate-binding module family 18 (CBM18) (also known as chitin binding 1 or chitin recognition protein) is found in a number of plant and fungalproteins that bindN-acetylglucosamine (e.g. solanaceouslectins of tomato and potato, plant endochitinases, the wound-induced proteins: hevein, win1 and win2, and the Kluyveromyces lactis killer toxin alpha subunit). The domain may occur in one or more copies and is thought to be involved in recognition or binding of chitin subunits. In chitinases, as well as in the potato wound-induced proteins, this 43-residue domain directly follows the signal sequence and is therefore at the N terminus of the mature protein; in the killer toxin alpha subunit it is located in the central section of the protein.
Carbohydrate-binding module family 27 (CBM27) binds to beta-1,4-mannooligosaccharides, carobgalactomannan, and konjac glucomannan, but not to cellulose (insoluble and soluble) or soluble birchwood xylan. CBM27 adopts a beta sandwich structure comprising 13 beta strands with a single, small alpha-helix and a single metal atom.
Carbohydrate-binding module family 28 (CBM28) does not compete with CBM17 modules when binding to non-crystalline cellulose. Different CBMs have been shown to bind to different sirtes in amorphous cellulose, CBM17 and CBM28 recognise distinct non-overlapping sites in amorphous cellulose. CBM28 has a "beta-jelly roll" topology, which is similar in structure to the CBM17 domains. Sequence and structural conservation in families CBM17 and CBM28 suggests that they have evolved through gene duplication and subsequent divergence.
Carbohydrate-binding module family 33 (CBM33) is a chitin-binding domain. It has a budded fibronectin type III fold consisting of two beta-sheets, arranged as a beta-sheet sandwich and a bud consisting of three short helices, located between beta-strands 1 and 2. It binds chitin via conserved polar amino acids. This domain is found in isolation in baculoviral spheroidin and spindolin proteins.
Carbohydrate-binding module family 48 (CBM48) is often found in enzymes containing glycosyl hydrolase family 13 catalytic domains. It is found in a range of enzymes that act on branched substrates i.e. isoamylase, pullulanase and branching enzyme. Isoamylase hydrolyses 1,6-alpha-D-glucosidic branch linkages in glycogen, amylopectin and dextrin; 1,4-alpha-glucan branching enzyme functions in the formation of 1,6-glucosidic linkages of glycogen; and pullulanase is a starch-debranching enzyme. CBM48 binds glycogen.
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