| ProGT ID | ProGT4 (Toxin B) |
| Organism Information |
| Organism Name | Clostridium difficile VPI 10463 |
| Clinical Implication | Pathogenic |
| Domain | Bacteria |
| Classification | Phylum : Firmicutes
Class : Clostridia
Orders : Eubacteriales
Family : Peptostreptococcaceae
Genus : Clostridium
Species : difficle
Strain : VPI 10463 |
| Taxonomic ID (NCBI) | 1496 |
| Genome Information |
| Gene Information |
| Gene Name | toxB |
| NCBI Gene ID | 31352216 |
| NCBI Reference Sequence | X53138 |
| Protein information |
| Protein Name | Toxin B |
| UniProtKB/ SwissProt ID | P18177 |
| NCBI Ref Seq | WP_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 CDS | CAA37298.1. |
| Sequence length | 2366 AA |
| Subcellular Location | Host cell plasma membrane |
| Function in Native Organism | 1) It is a secretory glycosyltransferase which glycosylates the Rho family proteins of the host cell. |
| Potential Application | 1) 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 Information | 1) 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. |
| Glycosyltransferase Information |
| Glycosylation Type | O- (Thr) linked |
| CAZY Family | GT44 |
| EC Number (BRENDA) | 2.4.1.B62. 13625. |
| Mechanism of Glycan Transfer | Sequential |
| Donor Type | UDP-Glc |
| Donor Specificity | Nucleotide activated sugars |
| Glycan Information |
| Glycan transferred | Monosaccharide (Glc) |
| Method of Glycan Indentification | LC-ESI-MS and MS/MS |
| Experimental_strategies | In vitro |
| Acceptor Subtrate Information |
| Acceptor Substrate name | RhoA |
| Acceptor Substrate name | Rac1 |
| Acceptor Substrate name | Cdc42 |
| Acceptor Substrate name | RhoB |
| Litrature |
| Year Of Validation | 1995 |
| Reference | Just, I., Selzer, J., Wilm, M., Eichel-Streiber, C.V., Mann, M. and Aktories, K., 1995. Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature, 375(6531), pp.500-503.
|
| Corresponding Author | Institute of Pharmacology and Toxicology, University of the Saarland, Homburg / Saar, Germany.
|
| Reference | Genth, H., Aktories, K. and Just, I., 1999. Monoglucosylation of RhoA at threonine 37 blocks cytosol-membrane cycling. Journal of biological chemistry, 274(41), pp.29050-29056.
|
| Corresponding Author | Institute of Pharmacology and Toxicology, University of Freiburg, Hermann-Herder-Strasse 5, D-79104 Freiburg, Germany.
|
| Reference | Ho, J.G., Greco, A., Rupnik, M. and 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), pp.18373-18378.
|
| Corresponding Author | Alberta 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. and Ng, K.K., 2006. Carbohydrate recognition by Clostridium difficile toxin A. Nature structural & molecular biology, 13(5), pp.460-461.
|
| Corresponding Author | Alberta 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. and Lacy, D.B., 2009. Structure-function analysis of inositol hexakisphosphate-induced autoprocessing in Clostridium difficile toxin A. Journal of Biological Chemistry, 284(33), pp.21934-21940.
|
| Corresponding Author | Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232-2363, USA.
|
| Reference | Papatheodorou, P., Zamboglou, C., Genisyuerek, S., Guttenberg, G. and Aktories, K., 2010. Clostridial glucosylating toxins enter cells via clathrin-mediated endocytosis. PloS one, 5(5), p.e10673.
|
| Corresponding Author | Institute 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. and Minton, N.P., 2010. The role of toxin A and toxin B in Clostridium difficile infection. Nature, 467(7316), pp.711-713.
|
| Corresponding Author | Clostridia 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. and 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), pp.3085-3097.
|
| Corresponding Author | Novartis Vaccines and Diagnostics, Siena, Italy.
|
| Reference | Murase, T., Eugenio, L., Schorr, M., Hussack, G., Tanha, J., Kitova, E.N., Klassen, J.S. and Ng, K.K., 2014. Structural basis for antibody recognition in the receptor-binding domains of toxins A and B from Clostridium difficile. Journal of Biological Chemistry, 289(4), pp.2331-2343.
|
| Corresponding Author | Department 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. and 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), pp.1706-1721.
|
| Corresponding Author | Institute of Toxicology, Medical School Hannover, Hannover, Germany.
|
