New to the CAZy classification? Read this first.
Want to learn more about CAZypedia? Read the CAZypedia 10th anniversary article in Glycobiology.
Carbohydrate Binding Module Family 48
This page is currently under construction. This means that the Responsible Curator has deemed that the page's content is not quite up to CAZypedia's standards for full public consumption. All information should be considered to be under revision and may be subject to major changes.
- Authors: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^
- Responsible Curators: ^^^Stefan Janecek^^^ and ^^^Birte Svensson^^^
|CAZy DB link|
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 , maltooligosaccharides , maltoheptaose , β-cyclodextrin , single α-1,6-branched glucosyl, maltosyl and maltoteatraosyl maltoheptaose  and single α-1,6-branched glucosyl β-cyclodextrin .
There is a number of family CBM48 structures solved mostly by X-ray crystallography [1, 4, 6, 6, 7, 8], but also by NMR . The structure is a typical β-sandwich with one well-defined binding site . As seen in the β1 subunit of the rat AMP-activated protein kinase (AMPK) , 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  and starch excess4 (SEX4) protein  both from plants. Notably, in complexes of the rice starch branching enzyme  and the SEX4 protein  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 , but of these only the CBM48 from rice starch branching enzyme has been solved in complex with carbohydrate ligands .
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 . 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 . A C-terminal position is also found for CBM48 in FLO6, a protein involved in starch biosynthesis . With regard to sequence/structure relationships and the way of carbohydrate binding, the modules from the family GH48 are most closely related to those from the family CBM20  and, in a wider sense, also to those from families CBM21, CBM53 [35,36] and the recently established family CBM69 .
- 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  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 . The first CBM48 structure confirming its carbohydrate binding ability (a complex with β-cyclodextrin) was determined for the β1 subunit of the rat AMPK , but it is of note that at that time the family CBM48 was not established .
- Chaen K, Noguchi J, Omori T, Kakuta Y, and Kimura M. (2012). Crystal structure of the rice branching enzyme I (BEI) in complex with maltopentaose. Biochem Biophys Res Commun. 2012;424(3):508-11. DOI:10.1016/j.bbrc.2012.06.145 |
- Koay A, Woodcroft B, Petrie EJ, Yue H, Emanuelle S, Bieri M, Bailey MF, Hargreaves M, Park JT, Park KH, Ralph S, Neumann D, Stapleton D, and Gooley PR. (2010). AMPK beta subunits display isoform specific affinities for carbohydrates. FEBS Lett. 2010;584(15):3499-503. DOI:10.1016/j.febslet.2010.07.015 |
- Meekins DA, Raththagala M, Husodo S, White CJ, Guo HF, Kötting O, Vander Kooi CW, and Gentry MS. (2014). Phosphoglucan-bound structure of starch phosphatase Starch Excess4 reveals the mechanism for C6 specificity. Proc Natl Acad Sci U S A. 2014;111(20):7272-7. DOI:10.1073/pnas.1400757111 |
- Polekhina G, Gupta A, van Denderen BJ, Feil SC, Kemp BE, Stapleton D, and Parker MW. (2005). Structural basis for glycogen recognition by AMP-activated protein kinase. Structure. 2005;13(10):1453-62. DOI:10.1016/j.str.2005.07.008 |
- Mobbs JI, Koay A, Di Paolo A, Bieri M, Petrie EJ, Gorman MA, Doughty L, Parker MW, Stapleton DI, Griffin MD, and Gooley PR. (2015). Determinants of oligosaccharide specificity of the carbohydrate-binding modules of AMP-activated protein kinase. Biochem J. 2015;468(2):245-57. DOI:10.1042/BJ20150270 |
- 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 |
- Møller MS, Windahl MS, Sim L, Bøjstrup M, Abou Hachem M, Hindsgaul O, Palcic M, Svensson B, and Henriksen A. (2015). Oligosaccharide and substrate binding in the starch debranching enzyme barley limit dextrinase. J Mol Biol. 2015;427(6 Pt B):1263-1277. DOI:10.1016/j.jmb.2014.12.019 |
- Janeček Š, Svensson B, and MacGregor EA. (2011). Structural and evolutionary aspects of two families of non-catalytic domains present in starch and glycogen binding proteins from microbes, plants and animals. Enzyme Microb Technol. 2011;49(5):429-40. DOI:10.1016/j.enzmictec.2011.07.002 |
- Feese MD, Kato Y, Tamada T, Kato M, Komeda T, Miura Y, Hirose M, Hondo K, Kobayashi K, and Kuroki R. (2000). Crystal structure of glycosyltrehalose trehalohydrolase from the hyperthermophilic archaeum Sulfolobus solfataricus. J Mol Biol. 2000;301(2):451-64. DOI:10.1006/jmbi.2000.3977 |
- 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 |
- Timmins J, Leiros HK, Leonard G, Leiros I, and McSweeney S. (2005). Crystal structure of maltooligosyltrehalose trehalohydrolase from Deinococcus radiodurans in complex with disaccharides. J Mol Biol. 2005;347(5):949-63. DOI:10.1016/j.jmb.2005.02.011 |
- Leiros HK, Timmins J, Ravelli RB, and McSweeney SM. (2006). Is radiation damage dependent on the dose rate used during macromolecular crystallography data collection?. Acta Crystallogr D Biol Crystallogr. 2006;62(Pt 2):125-32. DOI:10.1107/S0907444905033627 |
- 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 |
- Amodeo GA, Rudolph MJ, and Tong L. (2007). Crystal structure of the heterotrimer core of Saccharomyces cerevisiae AMPK homologue SNF1. Nature. 2007;449(7161):492-5. DOI:10.1038/nature06127 |
- 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 |
- Gourlay LJ, Santi I, Pezzicoli A, Grandi G, Soriani M, and Bolognesi M. (2009). Group B streptococcus pullulanase crystal structures in the context of a novel strategy for vaccine development. J Bacteriol. 2009;191(11):3544-52. DOI:10.1128/JB.01755-08 |
- Turkenburg JP, Brzozowski AM, Svendsen A, Borchert TV, Davies GJ, and Wilson KS. (2009). Structure of a pullulanase from Bacillus acidopullulyticus. Proteins. 2009;76(2):516-9. DOI:10.1002/prot.22416 |
- Pal K, Kumar S, Sharma S, Garg SK, Alam MS, Xu HE, Agrawal P, and Swaminathan K. (2010). Crystal structure of full-length Mycobacterium tuberculosis H37Rv glycogen branching enzyme: insights of N-terminal beta-sandwich in substrate specificity and enzymatic activity. J Biol Chem. 2010;285(27):20897-903. DOI:10.1074/jbc.M110.121707 |
- Song HN, Jung TY, Park JT, Park BC, Myung PK, Boos W, Woo EJ, and Park KH. (2010). Structural rationale for the short branched substrate specificity of the glycogen debranching enzyme GlgX. Proteins. 2010;78(8):1847-55. DOI:10.1002/prot.22697 |
- 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 |
- Noguchi J, Chaen K, Vu NT, Akasaka T, Shimada H, Nakashima T, Nishi A, Satoh H, Omori T, Kakuta Y, and Kimura M. (2011). Crystal structure of the branching enzyme I (BEI) from Oryza sativa L with implications for catalysis and substrate binding. Glycobiology. 2011;21(8):1108-16. DOI:10.1093/glycob/cwr049 |
- Møller MS, Abou Hachem M, Svensson B, and Henriksen A. (2012). Structure of the starch-debranching enzyme barley limit dextrinase reveals homology of the N-terminal domain to CBM21. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012;68(Pt 9):1008-12. DOI:10.1107/S1744309112031004 |
- Okazaki N, Tamada T, Feese MD, Kato M, Miura Y, Komeda T, Kobayashi K, Kondo K, Blaber M, and Kuroki R. (2012). Substrate recognition mechanism of a glycosyltrehalose trehalohydrolase from Sulfolobus solfataricus KM1. Protein Sci. 2012;21(4):539-52. DOI:10.1002/pro.2039 |
- Park JT, Song HN, Jung TY, Lee MH, Park SG, Woo EJ, and Park KH. (2013). A novel domain arrangement in a monomeric cyclodextrin-hydrolyzing enzyme from the hyperthermophile Pyrococcus furiosus. Biochim Biophys Acta. 2013;1834(1):380-6. DOI:10.1016/j.bbapap.2012.08.001 |
- Xiao B, Sanders MJ, Carmena D, Bright NJ, Haire LF, Underwood E, Patel BR, Heath RB, Walker PA, Hallen S, Giordanetto F, Martin SR, Carling D, and Gamblin SJ. (2013). Structural basis of AMPK regulation by small molecule activators. Nat Commun. 2013;4:3017. DOI:10.1038/ncomms4017 |
- Calabrese MF, Rajamohan F, Harris MS, Caspers NL, Magyar R, Withka JM, Wang H, Borzilleri KA, Sahasrabudhe PV, Hoth LR, Geoghegan KF, Han S, Brown J, Subashi TA, Reyes AR, Frisbie RK, Ward J, Miller RA, Landro JA, Londregan AT, Carpino PA, Cabral S, Smith AC, Conn EL, Cameron KO, Qiu X, and Kurumbail RG. (2014). Structural basis for AMPK activation: natural and synthetic ligands regulate kinase activity from opposite poles by different molecular mechanisms. Structure. 2014;22(8):1161-1172. DOI:10.1016/j.str.2014.06.009 |
- Sim L, Beeren SR, Findinier J, Dauvillée D, Ball SG, Henriksen A, and Palcic MM. (2014). Crystal structure of the Chlamydomonas starch debranching enzyme isoamylase ISA1 reveals insights into the mechanism of branch trimming and complex assembly. J Biol Chem. 2014;289(33):22991-23003. DOI:10.1074/jbc.M114.565044 |
- Xu J, Ren F, Huang CH, Zheng Y, Zhen J, Sun H, Ko TP, He M, Chen CC, Chan HC, Guo RT, Song H, and Ma Y. (2014). Functional and structural studies of pullulanase from Anoxybacillus sp. LM18-11. Proteins. 2014;82(9):1685-93. DOI:10.1002/prot.24498 |
- Li X, Wang L, Zhou XE, Ke J, de Waal PW, Gu X, Tan MH, Wang D, Wu D, Xu HE, and Melcher K. (2015). Structural basis of AMPK regulation by adenine nucleotides and glycogen. Cell Res. 2015;25(1):50-66. DOI:10.1038/cr.2014.150 |
- Møller MS, Vester-Christensen MB, Jensen JM, Hachem MA, Henriksen A, and Svensson B. (2015). Crystal structure of barley limit dextrinase-limit dextrinase inhibitor (LD-LDI) complex reveals insights into mechanism and diversity of cereal type inhibitors. J Biol Chem. 2015;290(20):12614-29. DOI:10.1074/jbc.M115.642777 |
- Palomo M, Kralj S, van der Maarel MJ, and Dijkhuizen L. (2009). The unique branching patterns of Deinococcus glycogen branching enzymes are determined by their N-terminal domains. Appl Environ Microbiol. 2009;75(5):1355-62. DOI:10.1128/AEM.02141-08 |
- Gentry MS, Dixon JE, and Worby CA. (2009). Lafora disease: insights into neurodegeneration from plant metabolism. Trends Biochem Sci. 2009;34(12):628-39. DOI:10.1016/j.tibs.2009.08.002 |
- Peng C, Wang Y, Liu F, Ren Y, Zhou K, Lv J, Zheng M, Zhao S, Zhang L, Wang C, Jiang L, Zhang X, Guo X, Bao Y, and Wan J. (2014). FLOURY ENDOSPERM6 encodes a CBM48 domain-containing protein involved in compound granule formation and starch synthesis in rice endosperm. Plant J. 2014;77(6):917-30. DOI:10.1111/tpj.12444 |
- Machovic M and Janecek S. (2006). The evolution of putative starch-binding domains. FEBS Lett. 2006;580(27):6349-56. DOI:10.1016/j.febslet.2006.10.041 |
- 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 |
- Peng H, Zheng Y, Chen M, Wang Y, Xiao Y, and Gao Y. (2014). A starch-binding domain identified in α-amylase (AmyP) represents a new family of carbohydrate-binding modules that contribute to enzymatic hydrolysis of soluble starch. FEBS Lett. 2014;588(7):1161-7. DOI:10.1016/j.febslet.2014.02.050 |
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)
- 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 |
- 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 |