Carbohydrate Binding Module Family 41

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• Author: ^^^Alicia Lammerts van Bueren^^^
• Responsible Curator: ^^^Al Boraston^^^

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CAZy DB link

http://www.cazy.org/CBM41.html

Ligand specificities

Modules from family CBM41 bind to alpha-glucans including starch, glycogen, amylose, amylopectin and pullulan, and shorter alpha glucan oligosaccharides derrived from these ploysaccharides including maltose, maltotriose and longer maltooligosaccharides up to DP7, glucosyl-maltotriose and glucosyl-maltotriosyl-maltotriose [1]. In larger polysaccharides CBM41 modules are specific for alpha-1,4-linked glucose chains but can also accommodate a linear alpha-1,6-linked glucose moiety. CBM41 modules are linked to alpha-glucan degrading enzymes from family GH13, exclusively with pullulanases (EC 3.2.1.41 GH13 subfamily 14) and starch/glycogen debranching enzymes (GH13 subfamily 12).

Structural Features

To date there are 11 X-ray crystal structures of CBM41 modules of which seven are in complex with carbohydrate ligand. CBM41 modules adopt a common beta-sandwich fold with the binding groove for alpha-glucans located on the face of the beta-sandwich fold. Typically two solvent exposed tryptophan residues form hydrophobic stacking interactions with the primary glucose molecule. The binding site includes 4 subsites that interact with up to 4 intra-chain glucose molecules, classifying them as Type B CBMs [2]. The mode of starch binding is similar to other starch-binding CBM families, including CBM20, 21, 34, 48. The fourth subsite in CBM41 from Thermotoga maritima was shown to accommodate either an alpha-1,4 or alpha-1,6-linked glucose residue, demonstrating that there is room for flexibility in the linkage that can be accommodated at the distal end of the binding pocket, making them distinct from other starch-binding module families [3].

The X-ray crystal structure of full length glycogen-debranching enzyme SpuA from Streptococcus pneumoniae revealed that the N-terminal CBM41 module directly participates in alpha-glucan substrate binding within the active sit of the of the adjoining GH13 catalytic module [4]. This is the first demonstration of a direct involvement of a CBM in substrate binding and thus far has only been found within this class of enzyme.

Content in this section should include, in paragraph form, a description of:

• Fold: Structural fold (beta trefoil, beta sandwich, etc.)
• Type: Include here Type A, B, or C and properties
• Features of ligand binding: Describe CBM binding pocket location (Side or apex) important residues for binding (W, Y, F, subsites), interact with reducing end, non-reducing end, planar surface or within polysaccharide chains. Include examples pdb codes. Metal ion dependent. Etc.

Functionalities

Content in this section should include, in paragraph form, a description of:

• Functional role of CBM: Describe common functional roles such as targeting, disruptive, anchoring, proximity/position on substrate.
• Most Common Associated Modules: 1. Glycoside Hydrolase Activity; 2. Additional Associated Modules (other CBM, FNIII, cohesin, dockerins, expansins, etc.)
• Novel Applications: Include here if CBM has been used to modify another enzyme, or if a CBM was used to label plant/mammalian tissues? Etc.

Family Firsts

First Identified

Family 41 CBMs were previously known as X28 modules. They were first classified as a CBM in 2004 after demonstrating alpha-glucan binding by an N-terminal X28 module from Thermotoga maritima pullulanase PulA [1]

First Structural Characterization

The first structure of CBM41 was revealed in the x-ray crystal structure of full-length pullulanase from Klebsiella pneumoniae [5].

References

1. Lammerts van Bueren A, Finn R, Ausió J, and Boraston AB. (2004). Alpha-glucan recognition by a new family of carbohydrate-binding modules found primarily in bacterial pathogens. Biochemistry. 2004;43(49):15633-42. DOI:10.1021/bi048215z |
2. Gilbert HJ, Knox JP, and Boraston AB. (2013). Advances in understanding the molecular basis of plant cell wall polysaccharide recognition by carbohydrate-binding modules. Curr Opin Struct Biol. 2013;23(5):669-77. DOI:10.1016/j.sbi.2013.05.005 |
3. van Bueren AL and Boraston AB. (2007). The structural basis of alpha-glucan recognition by a family 41 carbohydrate-binding module from Thermotoga maritima. J Mol Biol. 2007;365(3):555-60. DOI:10.1016/j.jmb.2006.10.018 |
4. Lammerts van Bueren A, Ficko-Blean E, Pluvinage B, Hehemann JH, Higgins MA, Deng L, Ogunniyi AD, Stroeher UH, El Warry N, Burke RD, Czjzek M, Paton JC, Vocadlo DJ, and Boraston AB. (2011). The conformation and function of a multimodular glycogen-degrading pneumococcal virulence factor. Structure. 2011;19(5):640-51. DOI:10.1016/j.str.2011.03.001 |
5. Mikami B, Iwamoto H, Malle D, Yoon HJ, Demirkan-Sarikaya E, Mezaki Y, and Katsuya Y. (2006). Crystal structure of pullulanase: evidence for parallel binding of oligosaccharides in the active site. J Mol Biol. 2006;359(3):690-707. DOI:10.1016/j.jmb.2006.03.058 |

6. Davies, G.J. and Sinnott, M.L. (2008) Sorting the diverse: the sequence-based classifications of carbohydrate-active enzymes. Biochem. J. (BJ Classic Paper, online only). DOI: 10.1042/BJ20080382

7. Boraston AB, Bolam DN, Gilbert HJ, and Davies GJ. (2004). Carbohydrate-binding modules: fine-tuning polysaccharide recognition. Biochem J. 2004;382(Pt 3):769-81. DOI:10.1042/BJ20040892 |
8. Hashimoto H (2006). Recent structural studies of carbohydrate-binding modules. Cell Mol Life Sci. 2006;63(24):2954-67. DOI:10.1007/s00018-006-6195-3 |
9. Shoseyov O, Shani Z, and Levy I. (2006). Carbohydrate binding modules: biochemical properties and novel applications. Microbiol Mol Biol Rev. 2006;70(2):283-95. DOI:10.1128/MMBR.00028-05 |
10. Guillén D, Sánchez S, and Rodríguez-Sanoja R. (2010). Carbohydrate-binding domains: multiplicity of biological roles. Appl Microbiol Biotechnol. 2010;85(5):1241-9. DOI:10.1007/s00253-009-2331-y |