ProGT5 (TcsL)

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ProGT ID ProGT5 (TcsL)
Organism Information
Organism NameClostridium sordellii 6018
Clinical ImplicationPathogenic
DomainBacteria
Classification Phylum : Firmicutes
Class : Clostridia
Orders : Eubacteriales
Family : Peptostreptococcaceae
Genus : Clostridium
Species : sordellii
Strain : 6018
Taxonomic ID (NCBI)1505
Genome Information
Gene Information
Gene NametcsL
NCBI Reference SequenceX82638
Protein information
Protein NameTcsL 
UniProtKB/ SwissProt IDQ46342
UniProtKB Sequence>tr|Q46342|Q46342_PAESO Cytotoxin L OS=Paeniclostridium sordellii PE=1 SV=1 MNLVNKAQLQKMVYVKFRIQEDEYVAILNALEEYHNMSESSVVEKYLKLKDINNLTDNYL NTYKKSGRNKALKKFKEYLTMEVLELKNNSLTPVEKNLHFIWIGGQINDTAINYINQWKD VNSDYTVKVFYDSNAFLINTLKKTIVESATNNTLESFRENLNDPEFDYNKFYRKRMEIIY DKQKHFIDYYKSQIEENPEFIIDNIIKTYLSNEYSKDLEALNKYIEESLNKITANNGNDI RNLEKFADEDLVRLYNQELVERWNLAAASDILRISMLKEDGGVYLDVDILPGIQPDLFKS INKPDSITNTSWEMIKLEAIMKYKEYIPGYTSKNFDMLDEEVQRSFESALSSKSDKSEIF LPLDDIKVSPLEVKIAFANNSVINQALISLKDSYCSDLVINQIKNRYKILNDNLNPSINE GTDFNTTMKIFSDKLASISNEDNMMFMIKITNYLKVGFAPDVRSTINLSGPGVYTGAYQD LLMFKDNSTNIHLLEPELRNFEFPKTKISQLTEQEITSLWSFNQARAKSQFEEYKKGYFE GALGEDDNLDFAQNTVLDKDYVSKKILSSMKTRNKEYIHYIVQLQGDKISYEASCNLFSK DPYSSILYQKNIEGSETAYYYYVADAEIKEIDKYRIPYQISNKRNIKLTFIGHGKSEFNT DTFANLDVDSLSSEIETILNLAKADISPKYIEINLLGCNMFSYSISAEETYPGKLLLKIK DRVSELMPSISQDSITVSANQYEVRINEEGKREILDHSGKWINKEESIIKDISSKEYISF NPKENKIIVKSKYLHELSTLLQEIRNNANSSDIDLEKKVMLTECEINVASNIDRQIVEGR IEEAKNLTSDSINYIKNEFKLIESISDSLYDLKHQNGLDDSHFISFEDISKTENGFRIRF INKETGNSIFIETEKEIFSEYATHISKEISNIKDTIFDNVNGKLVKKVNLDAAHEVNTLN SAFFIQSLIEYNTTKESLSNLSVAMKVQVYAQLFSTGLNTITDASKVVELVSTALDETID LLPTLSEGLPIIATIIDGVSLGAAIKELSETNDPLLRQEIEAKIGIMAVNLTAASTAIVT SALGIASGFSILLVPLAGISAGIPSLVNNELILQDKATKVIDYFKHISLAETEGAFTLLD DKIIMPQDDLVLSEIDFNNNSITLGKCEIWRAEGGSGHTLTDDIDHFFSSPSITYRKPWL SIYDVLNIKKEKIDFSKDLMVLPNAPNRVFGYEMGWTPGFRSLDNDGTKLLDRIRDHYEG QFYWRYFAFIADALITKLKPRYEDTNVRINLDGNTRSFIVPVITTEQIRKNLSYSFYGSG GSYSLSLSPYNMNIDLNLVENDTWVIDVDNVVKNITIESDEIQKGELIENILSKLNIEDN KIILNNHTINFYGDINESNRFISLTFSILEDINIIIEIDLVSKSYKILLSGNCMKLIENS SDIQQKIDHIGFNGEHQKYIPYSYIDNETKYNGFIDYSKKEGLFTAEFSNESIIRNIYMP DSNNLFIYSSKDLKDIRIINKGDVKLLIGNYFKDDMKVSLSFTIEDTNTIKLNGVYLDEN GVAQILKFMNNAKSALNTSNSLMNFLESINIKNIFYNNLDPNIEFILDTNFIISGSNSIG QFELICDKDKNIQPYFINFKIKETSYTLYVGNRQNLIVEPSYHLDDSGNISSTVINFSQK YLYGIDRYVNKVIIAPNLYTDEINITPVYKPNYICPEVIILDANYINEKINVNINDLSIR YVWDNDGSDLILIANSEEDNQPQVKIRFVNVFKSDTAADKLSFNFSDKQDVSVSKIISTF SLAAYSDGFFDYEFGLVSLDNDYFYINSFGNMVSGLIYINDSLYYFKPPKNNLITGFTTI DGNKYYFDPTKSGAASIGEITIDGKDYYFNKQGILQVGVINTSDGLKYFAPAGTLDENLE GESVNFIGKLNIDGKIYYFEDNYRAAVEWKLLDDETYYFNPKTGEALKGLHQIGDNKYYF DDNGIMQTGFITINDKVFYFNNDGVMQVGYIEVNGKYFYFGKNGERQLGVFNTPDGFKFF GPKDDDLGTEEGELTLYNGILNFNGKIYFFDISNTAVVGWGTLDDGSTYYFDDNRAEACI GLTVINDCKYYFDDNGIRQLGFITINDNIFYFSESGKIELGYQNINGNYFYIDESGLVLI GVFDTPDGYKYFAPLNTVNDNIYGQAVKYSGLVRVNEDVYYFGETYKIETGWIENETDKY YFDPETKKAYKGINVVDDIKYYFDENGIMRTGLISFENNNYYFNEDGKMQFGYLNIKDKM FYFGKDGKMQIGVFNTPDGFKYFAHQNTLDENFEGESINYTGWLDLDGKRYYFTDEYIAA TGSLTIDGYNYYFDPDTAELVVSE
EMBL CDSCAA57959.1.
Sequence length2364 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) Site-directed mutagenesis Ile-383 and Gln-385 in C. sordellii lethal toxin to serine and alanine, resulting in the change of the donor substrate specificity from UDP-glucose to UDP-GlcNAc.
Glycosyltransferase Information
Glycosylation TypeO- (Thr) linked 
CAZY FamilyGT44
EC Number (BRENDA)2.4.1.B62. 1514. 
Mechanism of Glycan TransferSequential
Donor TypeUDP-Glc
Donor SpecificityNucleotide activated sugars
Glycan Information
Glycan transferredMonosaccharide (Glc) 
Experimental_strategiesIn vitro 
Acceptor Subtrate Information
Acceptor Substrate name RhoA
Acceptor Substrate name Rac1
Acceptor Substrate name Ras
Acceptor Substrate name Cdc42
Litrature
Year Of Validation1995 
Reference Green, G.A., Schué, V. and Monteil, H., 1995. Cloning and characterization of the cytotoxin L-encoding gene of Clostridium sordellii: homology with Clostridium difficile cytotoxin B. Gene, 161(1), pp.57-61.

Corresponding AuthorLaboratory of Bacterial Toxinology, University Louis-Pasteur, Strasbourg, France.
Reference Green, G.A., Schue, V., Girardot, R. and Monteil, H., 1996. Characterisation of an enterotoxin-negative, cytotoxin-positive strain of Clostridium sordellii. Journal of medical microbiology, 44(1), pp.60-64.

Corresponding Author Laboratory of Bacterial Toxinology, University Louis-Pasteur, Strasbourg, France.
Reference Jank, T., Ziegler, M.O., Schulz, G.E. and Aktories, K., 2008. Inhibition of the glucosyltransferase activity of clostridial Rho/Ras-glucosylating toxins by castanospermine. FEBS letters, 582(15), pp.2277-2282.

Corresponding AuthorInstitute of Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-University, Albertstrasse 25, Freiburg, Germany
Reference Ziegler, M.O., Jank, T., Aktories, K. and Schulz, G.E., 2008. Conformational changes and reaction of clostridial glycosylating toxins. Journal of molecular biology, 377(5), pp.1346-1356.

Corresponding AuthorInstitute of Organic Chemistry and Biochemistry, Albert-Ludwigs-University, Albertstr. 21, D-79104 Freiburg im Breisgau, Germany
Reference Huelsenbeck, S.C., Klose, I., Reichenbach, M., Huelsenbeck, J. and Genth, H., 2009. Distinct kinetics of (H/K/N) Ras glucosylation and Rac1 glucosylation catalysed by Clostridium sordellii lethal toxin. FEBS letters, 583(19), pp.3133-3139.

Corresponding AuthorInstitute of Toxicology, Hannover Medical School, D-30625 Hannover, Germany
Reference Varela Chavez, C., Haustant, G.M., Baron, B., England, P., Chenal, A., Pauillac, S., Blondel, A. and Popoff, M.R., 2016. The Tip of the Four N-Terminal ?-Helices of Clostridium sordellii Lethal Toxin Contains the Interaction Site with Membrane Phosphatidylserine Facilitating Small GTPases Glucosylation. Toxins, 8(4), p.90.

Corresponding AuthorInstitute of Toxicology, Hannover Medical School, D-30625 Hannover, Germany