In molecular biology, a carbohydrate-binding module (CBM) is a

protein domain In molecular biology, a protein domain is a region of a protein's Peptide, polypeptide chain that is self-stabilizing and that Protein folding, folds independently from the rest. Each domain forms a compact folded Protein tertiary structure, thre ...

found in

carbohydrate A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ...

-active enzymes (for example glycoside hydrolases). The majority of these domains have carbohydrate-binding activity. Some of these domains are found on cellulosomal scaffoldin proteins. CBMs were previously known as

cellulose Cellulose is an organic compound with the chemical formula, formula , a polysaccharide consisting of a linear chain of several hundred to many thousands of glycosidic bond, β(1→4) linked glucose, D-glucose units. Cellulose is an important s ...

-binding domains. CBMs are classified into numerous families, based on

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

sequence similarity. There are currently (June 2011) 64 families of CBM in the CAZy database. CBMs of

microbial A microorganism, or microbe, is an organism of microscopic size, which may exist in its single-celled form or as a colony of cells. The possible existence of unseen microbial life was suspected from antiquity, with an early attestation in ...

glycoside hydrolase In biochemistry, glycoside hydrolases (also called glycosidases or glycosyl hydrolases) are a class of enzymes which catalysis, catalyze the hydrolysis of glycosidic bonds in polysaccharide, complex sugars. They are extremely common enzymes, wi ...

s play a central role in the recycling of photosynthetically fixed

carbon Carbon () is a chemical element; it has chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetravalent—meaning that its atoms are able to form up to four covalent bonds due to its valence shell exhibiting 4 ...

through their binding to specific

plant Plants are the eukaryotes that form the Kingdom (biology), kingdom Plantae; they are predominantly Photosynthesis, photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with c ...

structural

polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long-chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with wat ...

s. CBMs can recognise both crystalline and amorphous cellulose forms. CBMs are the most common non-catalytic modules associated with

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s active in plant cell-wall

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

. Many putative CBMs have been identified by

amino acid sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...

alignment Alignment may refer to: Archaeology * Alignment (archaeology), a co-linear arrangement of features or structures with external landmarks * Stone alignment, a linear arrangement of upright, parallel megalithic standing stones Biology * Struc ...

s but only a few representatives have been shown experimentally to have a carbohydrate-binding function.

CBM1

Carbohydrate-binding module family 1 (CBM1) consists of 36 amino acids. This domain contains 4 conserved

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

residues which are involved in the formation of two

disulfide bonds In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In in ...

CBM2

Carbohydrate-binding module family 2 (CBM2) contains two conserved

s - one at each extremity of the domain - which have been shown to be involved in a

disulfide bond In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inor ...

. There are also four conserved

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...

s, two of which are involved in cellulose binding.

CBM3

Carbohydrate-binding module family 3 (CBM3) is involved in

binding and is found associated with a wide range of

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

l glycosyl hydrolases. The

structure A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

of this domain is known; it forms a beta sandwich.

CBM4

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 Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are disturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with a ...

(NMR) spectroscopy was used to determine the

tertiary structure Protein tertiary structure is the three-dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains and the ...

of the 152

N-terminal cellulose-binding domain from ''C. fimi'' 1,4-beta-glucanase CenC (CBDN1). The tertiary

of CBDN1 is strikingly similar to that of the bacterial 1,3-1,4-beta-glucanases, as well as other sugar-binding

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s with jelly-roll folds. CBM4 and CBM9 are closely related.

CBM5

Carbohydrate-binding module family 5 (CBM5) binds chitin. CBM5 and CBM12 are distantly related.

CBM6

Carbohydrate-binding module family 6 (CBM6) is unusual in that it 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 substrate-binding clefts. Both cleft A and cleft B can bind cello-

oligosaccharides An oligosaccharide (; ) is a saccharide polymer containing a small number (typically three to ten) of monosaccharides (simple sugars). Oligosaccharides can have many functions including cell recognition and cell adhesion. They are normally presen ...

laminarin The molecule laminarin (also known as laminaran) is a storage glucan (a polysaccharide of glucose) found in brown algae. It is used as a carbohydrate food reserve in the same way that chrysolaminarin is used by phytoplankton, especially in diat ...

preferentially binds in cleft A, xylooligosaccharides only bind in cleft A and beta1,4,-beta1,3-mixed linked glucans only bind in cleft B.

CBM9

Carbohydrate-binding module family 9 (CBM9) binds to crystalline cellulose. CBM4 and CBM9 are closely related.

CBM10

Carbohydrate-binding module family 10 (CBM10) is found in two distinct sets of

s 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

. In anaerobic

that degrade plant cell walls, exemplified by '' Clostridium thermocellum'', the dockerin domains of the

catalytic Catalysis () is the increase in reaction rate, rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst ...

polypeptides Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ami ...

can bind equally well to any

cohesin Cohesin is a protein complex that mediates Establishment of sister chromatid cohesion, sister chromatid cohesion, homologous recombination, and Topologically associating domain, DNA looping. Cohesin is formed of SMC3, SMC1A, SMC1, RAD21, SCC1 an ...

from the same

organism An organism is any life, living thing that functions as an individual. Such a definition raises more problems than it solves, not least because the concept of an individual is also difficult. Many criteria, few of them widely accepted, have be ...

. More recently, anaerobic fungi, typified by ''Piromyces equi'', have been suggested to also synthesise a cellulosome complex, although the dockerin sequences of the

l and

fungal A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as one of the tradit ...

enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...

are completely different. For example, the fungal enzymes contain one, two or three copies of the dockerin

sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is cal ...

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 hand The EF hand is a helix–loop–helix structural domain or ''motif'' found in a large family of calcium-binding proteins. The EF-hand motif contains a helix–loop–helix topology, much like the spread thumb and forefinger of the human hand, in ...

s (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 A species () is often defined as the largest group of organisms in which any two individuals of the appropriate sexes or mating types can produce fertile offspring, typically by sexual reproduction. It is the basic unit of Taxonomy (biology), ...

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.

CBM11

Carbohydrate-binding module family 11 (CBM11) is found in a number of bacterial

cellulases Cellulase (; systematic name 4-β-D-glucan 4-glucanohydrolase) is any of several enzymes produced chiefly by fungi, bacteria, and protozoans that catalyze cellulolysis, the decomposition of cellulose and of some related polysaccharides: : End ...

. 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.

CBM12

Carbohydrate-binding module family 12 (CBM12) comprises two

beta-sheet The beta sheet (β-sheet, also β-pleated sheet) is a common structural motif, motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone chain, backbon ...

s, consisting of two and three antiparallel beta strands respectively. It binds chitin via the aromatic rings of

residues. CBM5 and CBM12 are distantly related.

CBM14

Carbohydrate-binding module family 14 (CBM14) is also known as the peritrophin-A domain. It is found in

chitin Chitin (carbon, C8hydrogen, H13oxygen, O5nitrogen, N)n ( ) is a long-chain polymer of N-Acetylglucosamine, ''N''-acetylglucosamine, an amide derivative of glucose. Chitin is the second most abundant polysaccharide in nature (behind only cell ...

binding proteins, particularly the peritrophic matrix proteins of insects and animal

chitinase Chitinases (, chitodextrinase, 1,4-β-poly-N-acetylglucosaminidase, poly-β-glucosaminidase, β-1,4-poly-N-acetyl glucosamidinase, poly ,4-(N-acetyl-β-D-glucosaminide)glycanohydrolase, (1→4)-2-acetamido-2-deoxy-β-D-glucan glycanohydrola ...

s. Copies of the domain are also found in some baculoviruses. It is an

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

domain that contains six conserved

s that probably form three disulfide bridges. Chitin binding has been demonstrated for a protein containing only two of these domains.

CBM15

Carbohydrate-binding module family 15 (CBM15), found in bacterial enzymes, has been shown to bind to

xylan Xylan (; ) ( CAS number: 9014-63-5) is a type of hemicellulose, a polysaccharide consisting mainly of xylose residues. It is found in plants, in the secondary cell walls of dicots and all cell walls of grasses. Xylan is the third most abu ...

and xylooligosaccharides. It has a beta-jelly roll fold, with a groove on the concave surface of one of the

CBM17

Carbohydrate-binding module family 17 (CBM17) appears to have a very shallow binding cleft that may be more accessible to cellulose

chain A chain is a serial assembly of connected pieces, called links, typically made of metal, with an overall character similar to that of a rope in that it is flexible and curved in compression but linear, rigid, and load-bearing in tension. A ...

s 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 Evolution is the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...

through

gene duplication Gene duplication (or chromosomal duplication or gene amplification) is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene ...

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 sites in amorphous cellulose, CBM17 and CBM28 recognise distinct non-overlapping sites in amorphous cellulose.

CBM18

Carbohydrate-binding module family 18 (CBM18) (also known as chitin binding 1 or chitin recognition protein) is found in a number of

and

s that

bind BIND () is a suite of software for interacting with the Domain Name System (DNS). Its most prominent component, named (pronounced ''name-dee'': , short for ''name Daemon (computing), daemon''), performs both of the main DNS server roles, acting ...

N-acetylglucosamine (e.g. solanaceous

lectins Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in r ...

of tomato and potato, plant endochitinases, the wound-induced proteins: hevein, win1 and win2, and the '' Kluyveromyces lactis'' killer

toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

alpha subunit). The domain may occur in one or more copies and is thought to be involved in recognition or binding of

subunits. In chitinases, as well as in the

potato The potato () is a starchy tuberous vegetable native to the Americas that is consumed as a staple food in many parts of the world. Potatoes are underground stem tubers of the plant ''Solanum tuberosum'', a perennial in the nightshade famil ...

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.

CBM19

Carbohydrate-binding module family 19 (CBM19), found in fungal

s, binds

CBM20

Carbohydrate-binding module family 20 (CBM20) binds to

starch Starch or amylum is a polymeric carbohydrate consisting of numerous glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants for energy storage. Worldwide, it is the most common carbohydrate in human diet ...

CBM21

Carbohydrate-binding module family 21 (CBM21), found in many

eukaryotic The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

proteins involved in

glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. It is the main storage form of glucose in the human body. Glycogen functions as one of three regularly used forms ...

metabolism, binds to glycogen.

CBM25

Carbohydrate-binding module family 25 (CBM25) binds alpha-glucooligosaccharides, particularly those containing alpha-1,6 linkages, and granular starch.

CBM27

Carbohydrate-binding module family 27 (CBM27) binds to beta-1,4-mannooligosaccharides,

carob The carob ( ; ''Ceratonia siliqua'') is a flowering evergreen tree or shrub in the Caesalpinioideae sub-family of the legume family, Fabaceae. It is widely cultivated for its edible fruit, which takes the form of seed pods, and as an ornam ...

galactomannan, and konjac glucomannan, but not to cellulose (insoluble and soluble) or soluble birchwood xylan. CBM27 adopts a beta sandwich structure comprising 13

beta strand The beta sheet (β-sheet, also β-pleated sheet) is a common structural motif, motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone chain, backbon ...

s with a single, small alpha-helix and a single metal

atom Atoms are the basic particles of the chemical elements. An atom consists of a atomic nucleus, nucleus of protons and generally neutrons, surrounded by an electromagnetically bound swarm of electrons. The chemical elements are distinguished fr ...

CBM28

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

through

and subsequent divergence.

CBM32

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.Ficko-Blean, Elizabeth; Boraston, Alisdair
"Carbohydrate Binding Module Family 32"CAZypedia
, 4 May 2017. CBM32 modules are associated with catalytic modules such as sialidases, B-N-acetylglucosaminidases, α-N-acetylglucosaminidases, mannanases and galactose oxidases.

CBM33

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 proteins.

CBM48

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

that act on branched substrates i.e. isoamylase, pullulanase and branching enzyme. Isoamylase hydrolyses 1,6-alpha-D-glucosidic branch linkages in glycogen,

amylopectin Amylopectin is a water-insoluble polysaccharide and highly branched polymer of α-glucose units found in plants. It is one of the two components of starch, the other being amylose. Plants store starch within specialized organelles called amyloplas ...

and

dextrin Dextrins are a group of low-molecular-weight carbohydrates produced by the hydrolysis of starch and glycogen. Dextrins are mixtures of polymers of D-glucose units linked by α-(1→4) or α-(1→6) glycosidic bonds. Dextrins can be produced fro ...

; 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.

CBM49

Carbohydrate-binding module family 49 (CBM49) is found at the C-terminal of cellulases and ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' binding studies have shown it to binds to crystalline cellulose.

References

External links

CAZy Carbohydrate binding modules
{{InterPro content, IPR001002 Protein domains Protein superfamilies