Carbohydrate Binding Module Family 48

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• Authors: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^
• Responsible Curators: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^

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CAZy DB link

https://www.cazy.org/CBM48.html

Ligand specificities

Family CBM48 contains modules able to bind various linear and cyclic α-glucans related to and derived from starch and glycogen having both the α-1,4- and α-1,6-linkages including, e.g., glucose and maltopentaose [1], maltooligosaccharides [2], maltoheptaose [3], β-cyclodextrin [4], single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose [2] and single α-1,6-branched glucosyl β-cyclodextrin [5].

Structural Features

There is a number of family CBM48 structures solved mostly by X-ray crystallography [1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30], but also by NMR [5]. The structure is a typical β-sandwich with one well-defined binding site [4]. As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) [4], the crucial role in binding is played by residues W100, F112, K126 and W133. As a complex exhibiting carbohydrate binding, the CBM48 has been determined only for β-subunits of mammalian AMPK [2, 4, 5], and family GH13 branching enzyme [1] and starch excess4 (SEX4) protein [3] both from plants. Notably, in complexes of the rice starch branching enzyme [1] and the SEX4 protein [3] with maltopentaose and maltoheptaose, respectively, the ligand interacts with both the CBM48 and the catalytic domain. In this light CBM48 possesses two binding sites including a canonical site 1 seen in the closely related CBM20 and which in CBM48 is occupied by ligands that at the same time interact with the active site area of the catalytic domain. There are many homologous CBM48 structures present in several enzyme specificities from the α-amylase family GH13 [31], but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands [1].

Functionalities

The CBM48 in amylolytic enzymes from the family GH13 precedes the catalytic TIM-barrel. This is the case of isoamylase [6, 26], maltooligosyltrehalohydrolase [7, 9, 10], branching enzyme [1, 8, 16, 20, 32], debranching enzyme [13, 17], pullulanase [11, 14, 15, 27], limit dextrinase [19, 21, 29, 30] and a bifunctional α-amylase/cyclomaltodextrinase [23]. In the non-amylolytic SEX4 proteins from plants and green algae, the module is positioned C-terminally with respect to the catalytic glucan phosphatase domain [3, 18, 33]. A special case is represented by mammalian AMPKs that possess the CBM48 within the β-subunits of its αβγ heterotrimer molecule [2, 4, 5, 24, 25, 28]; the same applies for AMPK’s yeast homologue SNF1 [12]. A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis [34]. With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family CBM48 are most closely related to those from the family CBM20 [31] and, in a wider sense, also to those from families CBM21, CBM53 [35, 36] and the recently established family CBM69 [37].

Family Firsts

First Identified

The family CBM48 was first referred to as (CBM20+CBM21)-related groups based on the in silico analysis of various proteins and taxa [35] and then defined within the CAZy database as an independent CBM family [38,39].

First Structural Characterization

Based on current knowledge [31,38,39], the first CBM48 structure without any carbohydrate bound was solved as the N-terminal domain of the isoamylase from Pseudomonas amyloderamosa [6]. The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK [4], but it is of note that at that time the family CBM48 was not established [40].

References

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6. Katsuya Y, Mezaki Y, Kubota M, and Matsuura Y. (1998). Three-dimensional structure of Pseudomonas isoamylase at 2.2 A resolution. J Mol Biol. 1998;281(5):885-97. DOI:10.1006/jmbi.1998.1992 |
8. Abad MC, Binderup K, Rios-Steiner J, Arni RK, Preiss J, and Geiger JH. (2002). The X-ray crystallographic structure of Escherichia coli branching enzyme. J Biol Chem. 2002;277(44):42164-70. DOI:10.1074/jbc.M205746200 |
11. 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 |
13. Woo EJ, Lee S, Cha H, Park JT, Yoon SM, Song HN, and Park KH. (2008). Structural insight into the bifunctional mechanism of the glycogen-debranching enzyme TreX from the archaeon Sulfolobus solfataricus. J Biol Chem. 2008;283(42):28641-8. DOI:10.1074/jbc.M802560200 |
19. Vester-Christensen MB, Abou Hachem M, Svensson B, and Henriksen A. (2010). Crystal structure of an essential enzyme in seed starch degradation: barley limit dextrinase in complex with cyclodextrins. J Mol Biol. 2010;403(5):739-50. DOI:10.1016/j.jmb.2010.09.031 |
36. Christiansen C, Abou Hachem M, Janecek S, Viksø-Nielsen A, Blennow A, and Svensson B. (2009). The carbohydrate-binding module family 20--diversity, structure, and function. FEBS J. 2009;276(18):5006-29. DOI:10.1111/j.1742-4658.2009.07221.x |

38. Machovic M, and Janecek S. “Domain evolution in the GH13 pullulanase subfamily with focus on the carbohydrate-binding module family 48.” Biologia 2008; 63: 1057-68. (DOI: 10.2478/s11756-008-0162-4)

39. Cantarel BL, Coutinho PM, Rancurel C, Bernard T, Lombard V, and Henrissat B. (2009). The Carbohydrate-Active EnZymes database (CAZy): an expert resource for Glycogenomics. Nucleic Acids Res. 2009;37(Database issue):D233-8. DOI:10.1093/nar/gkn663 |
40. Machovic M and Janecek S. (2006). Starch-binding domains in the post-genome era. Cell Mol Life Sci. 2006;63(23):2710-24. DOI:10.1007/s00018-006-6246-9 |