ProGT4 (Toxin B)
| ProGT ID | ProGT4 (Toxin B) |
| Organism Information | |
| Organism Name | Clostridium difficile VPI 10463 |
| Clinical Implication | Pathogenic |
| Domain | Bacteria |
| Phylum | Firmicutes |
| Classification | Family: Clostridiaceae Order: Clostridiales Class: Clostridia Phylum: Firmicutes |
| Taxonomic ID (NCBI) | 1496 |
| Genome Information | |
| Gene Information | |
| Gene Name | toxB |
| NCBI Gene ID | 31352216 |
| NCBI Reference Sequence | X53138 |
| Protein information | |
| Protein Name | Toxin BÂ |
| 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. |
| PDB ID | 2BVL[A] 2BVM[A] 4NC2 4NP4 5UQM 5UQN 5UQT |
| 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 | Nucleotide activated sugars |
| Donor Specificity | UDP-Glc |
| Glycan Information | |
| Glycan transferred | Monosaccharide (Glc)Â |
| 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 | 1995Â |
| 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 groups | Institute of Pharmacology and Toxicology, University of the Saarland, Homburg / Saar, Germany. |
| Corresponding Author | Aktories, K. |
| Contacts | Institute 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 groups | Institute of Pharmacology and Toxicology, University of Freiburg, Hermann-Herder-Strasse 5, D-79104 Freiburg, Germany. |
| Corresponding Author | Just, I. |
| Contacts | Institute 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 groups | Alberta Ingenuity Centre for Carbohydrate Sciences, Department of Biological Sciences, University of Calgary, Calgary, AB, Canada |
| Corresponding Author | Ng, K. K. S. |
| Contacts | 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., & 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 groups | Alberta Ingenuity Centre for Carbohydrate Sciences, Department of Biological Sciences, University of Calgary, Calgary, AB, Canada |
| Corresponding Author | Ng, K. K. |
| Contacts | 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., & 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 groups | Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232-2363, USA. |
| Corresponding Author | Lacy, D. B. |
| Contacts | Department 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 groups | Institute for Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-University Freiburg, Freiburg, Germany. |
| Corresponding Author | Aktories, K. |
| Contacts | 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., & 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 groups | 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 |
| Corresponding Author | Minton, N. P. |
| Contacts | 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., & 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 groups | Novartis Vaccines and Diagnostics, Siena, Italy. |
| Corresponding Author | Martinelli, M. |
| Contacts | Novartis 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 groups | Department of Biological Sciences and Alberta Glycomics Centre, University of Calgary, Calgary, Alberta T2N 1N4, Canada. |
| Corresponding Author | Ng, K. K |
| Contacts | 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. & 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 groups | Institute of Toxicology, Medical School Hannover, Hannover, Germany. |
| Corresponding Author | c |
| Contacts | Institute of Toxicology, Medical School Hannover, Hannover, Germany. |