Latest update: September 24, 2018


ProGT4 (Toxin B)

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ProGT ID ProGT4 (Toxin B)
Organism Information
Organism NameClostridium difficile VPI 10463
Clinical ImplicationPathogenic
DomainBacteria
PhylumFirmicutes
ClassificationFamily: Clostridiaceae
Order: Clostridiales
Class: Clostridia
Phylum: Firmicutes
Taxonomic ID (NCBI)1496
Genome Information
Gene Information
Gene NametoxB
NCBI Gene ID31352216
NCBI Reference SequenceX53138
Protein information
Protein NameToxin B 
UniProtKB/ SwissProt IDP18177
NCBI Ref SeqWP_009902069.1.
UniProtKB Sequence>sp|P18177|TOXB_CLODI Toxin B OS=Clostridioides difficile GN=toxB PE=1 SV=3 MSLVNRKQLEKMANVRFRTQEDEYVAILDALEEYHNMSENTVVEKYLKLKDINSLTDIYI DTYKKSGRNKALKKFKEYLVTEVLELKNNNLTPVEKNLHFVWIGGQINDTAINYINQWKD VNSDYNVNVFYDSNAFLINTLKKTVVESAINDTLESFRENLNDPRFDYNKFFRKRMEIIY DKQKNFINYYKAQREENPELIIDDIVKTYLSNEYSKEIDELNTYIEESLNKITQNSGNDV RNFEEFKNGESFNLYEQELVERWNLAAASDILRISALKEIGGMYLDVDMLPGIQPDLFES IEKPSSVTVDFWEMTKLEAIMKYKEYIPEYTSEHFDMLDEEVQSSFESVLASKSDKSEIF SSLGDMEASPLEVKIAFNSKGIINQGLISVKDSYCSNLIVKQIENRYKILNNSLNPAISE DNDFNTTTNTFIDSIMAEANADNGRFMMELGKYLRVGFFPDVKTTINLSGPEAYAAAYQD LLMFKEGSMNIHLIEADLRNFEISKTNISQSTEQEMASLWSFDDARAKAQFEEYKRNYFE GSLGEDDNLDFSQNIVVDKEYLLEKISSLARSSERGYIHYIVQLQGDKISYEAACNLFAK TPYDSVLFQKNIEDSEIAYYYNPGDGEIQEIDKYKIPSIISDRPKIKLTFIGHGKDEFNT DIFAGFDVDSLSTEIEAAIDLAKEDISPKSIEINLLGCNMFSYSINVEETYPGKLLLKVK DKISELMPSISQDSIIVSANQYEVRINSEGRRELLDHSGEWINKEESIIKDISSKEYISF NPKENKITVKSKNLPELSTLLQEIRNNSNSSDIELEEKVMLTECEINVISNIDTQIVEER IEEAKNLTSDSINYIKDEFKLIESISDALCDLKQQNELEDSHFISFEDISETDEGFSIRF INKETGESIFVETEKTIFSEYANHITEEISKIKGTIFDTVNGKLVKKVNLDTTHEVNTLN AAFFIQSLIEYNSSKESLSNLSVAMKVQVYAQLFSTGLNTITDAAKVVELVSTALDETID LLPTLSEGLPIIATIIDGVSLGAAIKELSETSDPLLRQEIEAKIGIMAVNLTTATTAIIT SSLGIASGFSILLVPLAGISAGIPSLVNNELVLRDKATKVVDYFKHVSLVETEGVFTLLD DKIMMPQDDLVISEIDFNNNSIVLGKCEIWRMEGGSGHTVTDDIDHFFSAPSITYREPHL SIYDVLEVQKEELDLSKDLMVLPNAPNRVFAWETGWTPGLRSLENDGTKLLDRIRDNYEG EFYWRYFAFIADALITTLKPRYEDTNIRINLDSNTRSFIVPIITTEYIREKLSYSFYGSG GTYALSLSQYNMGINIELSESDVWIIDVDNVVRDVTIESDKIKKGDLIEGILSTLSIEEN KIILNSHEINFSGEVNGSNGFVSLTFSILEGINAIIEVDLLSKSYKLLISGELKILMLNS NHIQQKIDYIGFNSELQKNIPYSFVDSEGKENGFINGSTKEGLFVSELPDVVLISKVYMD DSKPSFGYYSNNLKDVKVITKDNVNILTGYYLKDDIKISLSLTLQDEKTIKLNSVHLDES GVAEILKFMNRKGNTNTSDSLMSFLESMNIKSIFVNFLQSNIKFILDANFIISGTTSIGQ FEFICDENDNIQPYFIKFNTLETNYTLYVGNRQNMIVEPNYDLDDSGDISSTVINFSQKY LYGIDSCVNKVVISPNIYTDEINITPVYETNNTYPEVIVLDANYINEKINVNINDLSIRY VWSNDGNDFILMSTSEENKVSQVKIRFVNVFKDKTLANKLSFNFSDKQDVPVSEIILSFT PSYYEDGLIGYDLGLVSLYNEKFYINNFGMMVSGLIYINDSLYYFKPPVNNLITGFVTVG DDKYYFNPINGGAASIGETIIDDKNYYFNQSGVLQTGVFSTEDGFKYFAPANTLDENLEG EAIDFTGKLIIDENIYYFDDNYRGAVEWKELDGEMHYFSPETGKAFKGLNQIGDYKYYFN SDGVMQKGFVSINDNKHYFDDSGVMKVGYTEIDGKHFYFAENGEMQIGVFNTEDGFKYFA HHNEDLGNEEGEEISYSGILNFNNKIYYFDDSFTAVVGWKDLEDGSKYYFDEDTAEAYIG LSLINDGQYYFNDDGIMQVGFVTINDKVFYFSDSGIIESGVQNIDDNYFYIDDNGIVQIG VFDTSDGYKYFAPANTVNDNIYGQAVEYSGLVRVGEDVYYFGETYTIETGWIYDMENESD KYYFNPETKKACKGINLIDDIKYYFDEKGIMRTGLISFENNNYYFNENGEMQFGYINIED KMFYFGEDGVMQIGVFNTPDGFKYFAHQNTLDENFEGESINYTGWLDLDEKRYYFTDEYI AATGSVIIDGEEYYFDPDTAQLVISE
EMBL CDSCAA37298.1.
Sequence length2366 AA
Subcellular LocationHost cell plasma membrane
Function in Native Organism 1) It is a secretory glycosyltransferase which glycosylates the Rho family proteins of the host cell.
Potential Application1) Castanospermine binds to Rho/Ras-glucosylating Clostridium sordellii lethal toxin and Clostridium di?cile toxin B and inhibits the effect of toxins therefore this compound has a potential lead structure for the development of therapeutic inhibitors of clostridial glucosylating toxins.
Additional Information1) Structural analysis of toxin B suggests that it has an additional 309 amino acid residues which may be involved in target specificity.
2) The changing of Ile-383 and Gln-385 in toxin B to serine and alanine, respectively, increased the utilization of UDP-N-acetylglucosamine as a sugar donor for modification of RhoA.
PDB ID 2BVL[A] 2BVM[A] 4NC2 4NP4 5UQM 5UQN 5UQT
Glycosyltransferase Information
Glycosylation TypeO- (Thr) linked 
CAZY FamilyGT44
EC Number (BRENDA)2.4.1.B62.13625.
Mechanism of Glycan TransferSequential
Donor TypeNucleotide activated sugars
Donor SpecificityUDP-Glc
Glycan Information
Glycan transferredMonosaccharide (Glc) 
Method of Glycan IndentificationLC-ESI-MS and MS/MS
Experimental_strategiesIn vitro 
Acceptor Subtrate Information
Acceptor Substrate name RhoA
Acceptor Substrate name Rac1
Acceptor Substrate name Cdc42
Acceptor Substrate name RhoB
Litrature
Year Of Validation1995 
Reference Just, I., Selzer, J., Wilm, M., Von Eichel-Streiber, C., Mann, M., & Aktories, K. (1995). Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature, 375(6531), 500.

Authors Just, I., Selzer, J., Wilm, M., Von Eichel-Streiber, C., Mann, M., & Aktories, K.
Research groupsInstitute of Pharmacology and Toxicology, University of the Saarland, Homburg / Saar, Germany.
Corresponding Author Aktories, K.
ContactsInstitute of Pharmacology and Toxicology, University of the Saarland, Homburg / Saar, Germany.
Reference Genth, H., Aktories, K., & Just, I. (1999). Monoglucosylation of RhoA at threonine 37 blocks cytosol-membrane cycling. Journal of biological chemistry, 274(41), 29050-29056.

Authors Genth, H., Aktories, K., & Just, I.
Research groupsInstitute of Pharmacology and Toxicology, University of Freiburg, Hermann-Herder-Strasse 5, D-79104 Freiburg, Germany.
Corresponding Author Just, I.
ContactsInstitute of Pharmacology and Toxicology, University of Freiburg, Hermann-Herder-Strasse 5, D-79104 Freiburg, Germany.
Reference Ho, J. G., Greco, A., Rupnik, M., & Ng, K. K. S. (2005). Crystal structure of receptor-binding C-terminal repeats from Clostridium difficile toxin A. Proceedings of the National Academy of Sciences, 102(51), 18373-18378.

Authors Ho, J. G., Greco, A., Rupnik, M., & Ng, K. K. S.
Research groupsAlberta Ingenuity Centre for Carbohydrate Sciences, Department of Biological Sciences, University of Calgary, Calgary, AB, Canada
Corresponding Author Ng, K. K. S.
ContactsAlberta Ingenuity Centre for Carbohydrate Sciences, Department of Biological Sciences, University of Calgary, Calgary, AB, Canada
Reference Greco, A., Ho, J. G., Lin, S. J., Palcic, M. M., Rupnik, M., & Ng, K. K. (2006). Carbohydrate recognition by Clostridium difficile toxin A. Nature Structural and Molecular Biology, 13(5), 460.

Authors Greco, A., Ho, J. G., Lin, S. J., Palcic, M. M., Rupnik, M., & Ng, K. K.
Research groupsAlberta Ingenuity Centre for Carbohydrate Sciences, Department of Biological Sciences, University of Calgary, Calgary, AB, Canada
Corresponding Author Ng, K. K.
ContactsAlberta Ingenuity Centre for Carbohydrate Sciences, Department of Biological Sciences, University of Calgary, Calgary, AB, Canada
Reference Pruitt, R. N., Chagot, B., Cover, M., Chazin, W. J., Spiller, B., & Lacy, D. B. (2009). Structure-function analysis of inositol hexakisphosphate-induced autoprocessing in Clostridium difficile toxin A. Journal of Biological Chemistry, 284(33), 21934-21940.

Authors Pruitt, R. N., Chagot, B., Cover, M., Chazin, W. J., Spiller, B., & Lacy, D. B.
Research groupsDepartment of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232-2363, USA.
Corresponding Author Lacy, D. B.
ContactsDepartment of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232-2363, USA.
Reference Papatheodorou, P., Zamboglou, C., Genisyuerek, S., Guttenberg, G., & Aktories, K. (2010). Clostridial glucosylating toxins enter cells via clathrin-mediated endocytosis. PloS one, 5(5), e10673.

Authors Papatheodorou, P., Zamboglou, C., Genisyuerek, S., Guttenberg, G., & Aktories, K.
Research groupsInstitute for Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
Corresponding Author Aktories, K.
ContactsInstitute for Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
Reference Kuehne, S. A., Cartman, S. T., Heap, J. T., Kelly, M. L., Cockayne, A., & Minton, N. P. (2010). The role of toxin A and toxin B in Clostridium difficile infection. Nature, 467(7316), 711

Authors Kuehne, S. A., Cartman, S. T., Heap, J. T., Kelly, M. L., Cockayne, A., & Minton, N. P.
Research groupsClostridia Research Group, Centre for Biomolecular Sciences, School of Molecular Medical Sciences, Nottingham Digestive Diseases Centre, NIHR Biomedical Research Unit, University of Nottingham, Nottingham NG7 2RD, UK
Corresponding AuthorMinton, N. P.
ContactsClostridia Research Group, Centre for Biomolecular Sciences, School of Molecular Medical Sciences, Nottingham Digestive Diseases Centre, NIHR Biomedical Research Unit, University of Nottingham, Nottingham NG7 2RD, UK
Reference D’urzo, N., Malito, E., Biancucci, M., Bottomley, M. J., Maione, D., Scarselli, M., & Martinelli, M. (2012). The structure of Clostridium difficile toxin A glucosyltransferase domain bound to Mn2+ and UDP provides insights into glucosyltransferase activity and product release. The FEBS journal, 279(17), 3085-3097.

Authors D’urzo, N., Malito, E., Biancucci, M., Bottomley, M. J., Maione, D., Scarselli, M., & Martinelli, M. 
Research groupsNovartis Vaccines and Diagnostics, Siena, Italy.
Corresponding AuthorMartinelli, M.
ContactsNovartis Vaccines and Diagnostics, Siena, Italy.
Reference Murase, T., Eugenio, L., Schorr, M., Hussack, G., Tanha, J., Kitova, E.N., Klassen, J.S. & Ng, K. K. (2013). Structural basis for antibody recognition in the receptor-binding domains of toxins A and B from Clostridium difficile. Journal of Biological Chemistry, jbc-M113.

Authors Murase, T., Eugenio, L., Schorr, M., Hussack, G., Tanha, J., Kitova, E.N., Klassen, J.S. & Ng, K. K
Research groupsDepartment of Biological Sciences and Alberta Glycomics Centre, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
Corresponding Author Ng, K. K
ContactsDepartment of Biological Sciences and Alberta Glycomics Centre, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
Reference Genth, H., Pauillac, S., Schelle, I., Bouvet, P., Bouchier, C., Varela?Chavez, C., Just, I. & Popoff, M. R. (2014). Haemorrhagic toxin and lethal toxin from C lostridium sordellii strain vpi9048: molecular characterization and comparative analysis of substrate specificity of the large clostridial glucosylating toxins. Cellular microbiology, 16(11), 1706-1721.

Authors Genth, H., Pauillac, S., Schelle, I., Bouvet, P., Bouchier, C., Varela?Chavez, C., Just, I. & Popoff, M. R.
Research groupsInstitute of Toxicology, Medical School Hannover, Hannover, Germany.
Corresponding Authorc
ContactsInstitute of Toxicology, Medical School Hannover, Hannover, Germany.