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 32 (CBM32) binds to diverse substrates, ranging from plant cell wall polysaccharides to complex glycans. The module has so far been found in microorganisms, including archea, eubacteria and fungi. CBM32 adopts a beta-sandwich fold and has a bound metal atom, most often observed to be calcium. CBM32 modules are associated with catalytic modules such as sialidases, B-N-acetylglucosaminidases, α-N-acetylglucosaminidases, mannanases and galactose oxidases.
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.
^ abSzabo, L.; Jamal, S.; Xie, H.; Charnock, S. J.; Bolam, D. N.; Gilbert, H. J.; Davies, G. J. (2001). "Structure of a Family 15 Carbohydrate-binding Module in Complex with Xylopentaose. Evidence that xylan binds in an approximate 3-fold helical conformation". Journal of Biological Chemistry. 276 (52): 49061–49065. doi:10.1074/jbc.M109558200. PMID11598143.
^ abcJamal S, Nurizzo D, Boraston AB, Davies GJ (May 2004). "X-ray crystal structure of a non-crystalline cellulose-specific carbohydrate-binding module: CBM28". J. Mol. Biol. 339 (2): 253–8. doi:10.1016/j.jmb.2004.03.069. PMID15136030.
^Roske Y, Sunna A, Pfeil W, Heinemann U (July 2004). "High-resolution crystal structures of Caldicellulosiruptor strain Rt8B.4 carbohydrate-binding module CBM27-1 and its complex with mannohexaose". J. Mol. Biol. 340 (3): 543–54. doi:10.1016/j.jmb.2004.04.072. PMID15210353.
^Gilkes NR, Claeyssens M, Aebersold R, Henrissat B, Meinke A, Morrison HD, Kilburn DG, Warren RA, Miller RC (December 1991). "Structural and functional relationships in two families of beta-1,4-glycanases". Eur. J. Biochem. 202 (2): 367–77. doi:10.1111/j.1432-1033.1991.tb16384.x. PMID1761039.
^Meinke A, Gilkes NR, Kilburn DG, Miller RC, Warren RA (December 1991). "Bacterial cellulose-binding domain-like sequences in eucaryotic polypeptides". Protein Seq. Data Anal. 4 (6): 349–53. PMID1812490.
^Simpson PJ, Xie H, Bolam DN, Gilbert HJ, Williamson MP (December 2000). "The structural basis for the ligand specificity of family 2 carbohydrate-binding modules". J. Biol. Chem. 275 (52): 41137–42. doi:10.1074/jbc.M006948200. PMID10973978.
^Xu, G. Y.; Ong, E.; Gilkes, N. R.; Kilburn, D. G.; Muhandiram, D. R.; Harris-Brandts, M.; Carver, J. P.; Kay, L. E.; Harvey, T. S. (1995). "Solution structure of a cellulose-binding domain from Cellulomonas fimi by nuclear magnetic resonance spectroscopy". Biochemistry. 34 (21): 6993–7009. doi:10.1021/bi00021a011. PMID7766609.
^Poole DM, Morag E, Lamed R, Bayer EA, Hazlewood GP, Gilbert HJ (December 1992). "Identification of the cellulose-binding domain of the cellulosome subunit S1 from Clostridium thermocellum YS". FEMS Microbiol. Lett. 78 (2–3): 181–6. doi:10.1016/0378-1097(92)90022-g. PMID1490597.
^Brun E, Johnson PE, Creagh AL, Tomme P, Webster P, Haynes CA, McIntosh LP (March 2000). "Structure and binding specificity of the second N-terminal cellulose-binding domain from Cellulomonas fimi endoglucanase C". Biochemistry. 39 (10): 2445–58. doi:10.1021/bi992079u. PMID10704194.
^Johnson PE, Joshi MD, Tomme P, Kilburn DG, McIntosh LP (November 1996). "Structure of the N-terminal cellulose-binding domain of Cellulomonas fimi CenC determined by nuclear magnetic resonance spectroscopy". Biochemistry. 35 (45): 14381–94. doi:10.1021/bi961612s. PMID8916925.
^ abAkagi, K. -I.; Watanabe, J.; Hara, M.; Kezuka, Y.; Chikaishi, E.; Yamaguchi, T.; Akutsu, H.; Nonaka, T.; Watanabe, T.; Ikegami, T. (2006). "Identification of the Substrate Interaction Region of the Chitin-Binding Domain of Streptomyces griseus Chitinase C". Journal of Biochemistry. 139 (3): 483–493. doi:10.1093/jb/mvj062. PMID16567413.
^Henshaw, J. L.; Bolam, D. N.; Pires, V. M.; Czjzek, M.; Henrissat, B.; Ferreira, L. M.; Fontes, C. M.; Gilbert, H. J. (2004). "The Family 6 Carbohydrate Binding Module CmCBM6-2 Contains Two Ligand-binding Sites with Distinct Specificities". Journal of Biological Chemistry. 279 (20): 21552–21559. doi:10.1074/jbc.M401620200. PMID15004011.
^Winterhalter, C.; Heinrich, P.; Candussio, A.; Wich, G.; Liebl, W. (1995). "Identification of a novel cellulose-binding domain within the multidomain 120 kDa xylanase XynA of the hyperthermophilic bacterium Thermotoga maritima". Molecular Microbiology. 15 (3): 431–444. doi:10.1111/j.1365-2958.1995.tb02257.x. PMID7783614.
^Fanutti C, Ponyi T, Black GW, Hazlewood GP, Gilbert HJ (December 1995). "The conserved noncatalytic 40-residue sequence in cellulases and hemicellulases from anaerobic fungi functions as a protein docking domain". J. Biol. Chem. 270 (49): 29314–22. doi:10.1074/jbc.270.49.29314. PMID7493964.
^ abRaghothama S, Eberhardt RY, Simpson P, Wigelsworth D, White P, Hazlewood GP, Nagy T, Gilbert HJ, Williamson MP (September 2001). "Characterization of a cellulosome dockerin domain from the anaerobic fungus Piromyces equi". Nat. Struct. Biol. 8 (9): 775–8. doi:10.1038/nsb0901-775. PMID11524680.
^ abCarvalho, A. L.; Goyal, A.; Prates, J. A.; Bolam, D. N.; Gilbert, H. J.; Pires, V. M.; Ferreira, L. M.; Planas, A.; Romão, M. J.; Fontes, C. M. (2004). "The Family 11 Carbohydrate-binding Module of Clostridium thermocellum Lic26A-Cel5E Accommodates -1,4- and -1,3-1,4-Mixed Linked Glucans at a Single Binding Site". Journal of Biological Chemistry. 279 (33): 34785–34793. doi:10.1074/jbc.M405867200. PMID15192099.
^ abShen Z, Jacobs-Lorena M (July 1998). "A type I peritrophic matrix protein from the malaria vector Anopheles gambiae binds to chitin. Cloning, expression, and characterization". J. Biol. Chem. 273 (28): 17665–70. doi:10.1074/jbc.273.28.17665. PMID9651363.
^Elvin CM, Vuocolo T, Pearson RD, East IJ, Riding GA, Eisemann CH, Tellam RL (April 1996). "Characterization of a major peritrophic membrane protein, peritrophin-44, from the larvae of Lucilia cuprina. cDNA and deduced amino acid sequences". J. Biol. Chem. 271 (15): 8925–35. doi:10.1074/jbc.271.15.8925. PMID8621536.
^Notenboom V, Boraston AB, Chiu P, Freelove AC, Kilburn DG, Rose DR (December 2001). "Recognition of cello-oligosaccharides by a family 17 carbohydrate-binding module: an X-ray crystallographic, thermodynamic and mutagenic study". J. Mol. Biol. 314 (4): 797–806. doi:10.1006/jmbi.2001.5153. PMID11733998.
^ abJamal, S.; Nurizzo, D.; Boraston, A. B.; Davies, G. J. (2004). "X-ray Crystal Structure of a Non-crystalline Cellulose-specific Carbohydrate-binding Module: CBM28". Journal of Molecular Biology. 339 (2): 253–258. doi:10.1016/j.jmb.2004.03.069. PMID15136030.
^Wright HT, Sandrasegaram G, Wright CS (September 1991). "Evolution of a family of N-acetylglucosamine binding proteins containing the disulfide-rich domain of wheat germ agglutinin". J. Mol. Evol. 33 (3): 283–94. doi:10.1007/bf02100680. PMID1757999.
^Lerner DR, Raikhel NV (June 1992). "The gene for stinging nettle lectin (Urtica dioica agglutinin) encodes both a lectin and a chitinase". J. Biol. Chem. 267 (16): 11085–91. PMID1375935.
^Kuranda, M. J.; Robbins, P. W. (1991). "Chitinase is required for cell separation during growth of Saccharomyces cerevisiae". The Journal of Biological Chemistry. 266 (29): 19758–19767. PMID1918080.
^Penninga, D.; Van Der Veen, B. A.; Knegtel, R. M.; Van Hijum, S. A.; Rozeboom, H. J.; Kalk, K. H.; Dijkstra, B. W.; Dijkhuizen, L. (1996). "The raw starch binding domain of cyclodextrin glycosyltransferase from Bacillus circulans strain 251". The Journal of Biological Chemistry. 271 (51): 32777–32784. doi:10.1074/jbc.271.51.32777. PMID8955113.
^Oyama, T.; Kusunoki, M.; Kishimoto, Y.; Takasaki, Y.; Nitta, Y. (1999). "Crystal structure of beta-amylase from Bacillus cereus var. Mycoides at 2.2 a resolution". Journal of Biochemistry. 125 (6): 1120–1130. doi:10.1093/oxfordjournals.jbchem.a022394. PMID10348915.
^Boraston, A. B.; Healey, M.; Klassen, J.; Ficko-Blean, E.; Lammerts Van Bueren, A.; Law, V. (2005). "A Structural and Functional Analysis of -Glucan Recognition by Family 25 and 26 Carbohydrate-binding Modules Reveals a Conserved Mode of Starch Recognition". Journal of Biological Chemistry. 281 (1): 587–598. doi:10.1074/jbc.M509958200. PMID16230347.
^Boraston AB, Revett TJ, Boraston CM, Nurizzo D, Davies GJ (June 2003). "Structural and thermodynamic dissection of specific mannan recognition by a carbohydrate binding module, TmCBM27". Structure. 11 (6): 665–75. doi:10.1016/S0969-2126(03)00100-X. PMID12791255.
^ abAbbot, DW; Eirin-Lopez, JM; Boraston, AB (January 2008). "Insight into ligand diversity and novel biological roles for family 32 carbohydrate-binding modules". Molecular Biology and Evolution. 25 (1): 155–67. doi:10.1093/molbev/msm243. PMID18032406.
^Schnellmann, J.; Zeltins, A.; Blaak, H.; Schrempf, H. (1994). "The novel lectin-like protein CHB1 is encoded by a chitin-inducible Streptomyces olivaceoviridis gene and binds specifically to crystalline alpha-chitin of fungi and other organisms". Molecular Microbiology. 13 (5): 807–819. doi:10.1111/j.1365-2958.1994.tb00473.x. PMID7815940.
^Vaaje-Kolstad, G.; Houston, D. R.; Riemen, A. H.; Eijsink, V. G.; Van Aalten, D. M. (2005). "Crystal Structure and Binding Properties of the Serratia marcescens Chitin-binding Protein CBP21". Journal of Biological Chemistry. 280 (12): 11313–11319. doi:10.1074/jbc.M407175200. PMID15590674.
^Katsuya, Y.; Mezaki, Y.; Kubota, M.; Matsuura, Y. (1998). "Three-dimensional structure of Pseudomonas isoamylase at 2.2 Å resolution1". Journal of Molecular Biology. 281 (5): 885–897. doi:10.1006/jmbi.1998.1992. PMID9719642.
^Polekhina, G.; Gupta, A.; Michell, B. J.; Van Denderen, B.; Murthy, S.; Feil, S. C.; Jennings, I. G.; Campbell, D. J.; Witters, L. A.; Parker, M. W.; Kemp, B. E.; Stapleton, D. (2003). "AMPK beta subunit targets metabolic stress sensing to glycogen". Current Biology. 13 (10): 867–871. doi:10.1016/S0960-9822(03)00292-6. PMID12747837.
^Hudson, E. R.; Pan, D. A.; James, J.; Lucocq, J. M.; Hawley, S. A.; Green, K. A.; Baba, O.; Terashima, T.; Hardie, D. G. (2003). "A novel domain in AMP-activated protein kinase causes glycogen storage bodies similar to those seen in hereditary cardiac arrhythmias". Current Biology. 13 (10): 861–866. doi:10.1016/S0960-9822(03)00249-5. PMID12747836.
^Urbanowicz BR, Catala C, Irwin D, Wilson DB, Ripoll DR, Rose JK (April 2007). "A tomato endo-beta-1,4-glucanase, SlCel9C1, represents a distinct subclass with a new family of carbohydrate binding modules (CBM49)". J. Biol. Chem. 282 (16): 12066–74. doi:10.1074/jbc.M607925200. PMID17322304.