7S0Z

Structures of TcdB in complex with R-Ras

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
B [auth A]	SCOP2B Superfamily	Nucleotide-diphospho-sugar transferases	8103504	3000077	SCOP2B (2022-06-29)
A [auth B]	SCOP2B Superfamily	Nucleotide-diphospho-sugar transferases	8103504	3000077	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Ras-like P-loop GTPases	8057362	3002022	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Ras-like P-loop GTPases	8057362	3002022	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
B [auth A]	MLD	e7s0zA2	A: alpha bundles	X: Bromodomain-like	H: PMT helical bundle domain-like	T: PMT helical bundle domain-like	F: MLD	ECOD (1.6)
B [auth A]	TcdA_TcdB	e7s0zA1	A: a/b three-layered sandwiches	X: Nucleotide-diphospho-sugar transferases (From Topology)	H: Nucleotide-diphospho-sugar transferases (From Topology)	T: Nucleotide-diphospho-sugar transferases	F: TcdA_TcdB	ECOD (1.6)
A [auth B]	MLD	e7s0zB2	A: alpha bundles	X: Bromodomain-like	H: PMT helical bundle domain-like	T: PMT helical bundle domain-like	F: MLD	ECOD (1.6)
A [auth B]	TcdA_TcdB	e7s0zB1	A: a/b three-layered sandwiches	X: Nucleotide-diphospho-sugar transferases (From Topology)	H: Nucleotide-diphospho-sugar transferases (From Topology)	T: Nucleotide-diphospho-sugar transferases	F: TcdA_TcdB	ECOD (1.6)
C	Ras	e7s0zC1	A: a/b three-layered sandwiches	X: P-loop domains-like	H: P-loop domains-related	T: P-loop containing nucleoside triphosphate hydrolases	F: Ras	ECOD (1.6)
D	Ras	e7s0zD1	A: a/b three-layered sandwiches	X: P-loop domains-like	H: P-loop domains-related	T: P-loop containing nucleoside triphosphate hydrolases	F: Ras	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A [auth B], B [auth A]	PF12919	TcdA/TcdB catalytic glycosyltransferase domain (TcdA_TcdB)	TcdA/TcdB catalytic glycosyltransferase domain	This domain represents the N-terminal glycosyltransferase from a set of toxins found in some bacteria. This domain in TcdB glycosylates the host RhoA protein.	Domain
A [auth B], B [auth A]	PF12918	TcdB toxin N-terminal helical domain (TcdB_N)	TcdB toxin N-terminal helical domain	This is a short helical bundle domain found associated with the catalytic domain of the TcdB toxin from C. difficile [1]. The function of this domain is unknown, but it may be involved in substrate recognition.	Domain
A [auth B], B [auth A]	PF11647	Membrane Localization Domain (MLD)	Membrane Localization Domain	This is a membrane localization domain found in multiple families of bacterial toxins including all of the clostridial glucosyltransferase toxins and various MARTX toxins (multifunctional-autoprocessing RTX toxins) [1,4]. In the Pasteurella multocida ...	This is a membrane localization domain found in multiple families of bacterial toxins including all of the clostridial glucosyltransferase toxins and various MARTX toxins (multifunctional-autoprocessing RTX toxins) [1,4]. In the Pasteurella multocida toxin (PMT) C-terminal fragment, structural analysis have indicated that the C1 domain possesses a signal that leads the toxin to the cell membrane. Furthermore, the C1 domain was found to structurally resemble the phospholipid-binding domain of C. difficile toxin B [2]. Functional studies in Vibrio cholera indicate that the subdomain at the N terminus of RID (Rho-inactivation domain), homologous to the membrane targeting C1 domain of Pasteurella multocida toxin, is a conserved membrane localization domain essential for proper localization [1]. The Rho-inactivation domain (RID) of MARTX (Multifunctional Autoprocessing RTX toxin) is responsible for inactivating the Rho-family of small GTPases in Vibrio cholerae. It is a bacterial toxin that self-process by a cysteine peptidase mechanism [3]. The Vibrio cholerae RTX toxin is an autoprocessing cysteine protease whose activity is stimulated by the intracellular environment [3]. This cysteine peptidase belongs to MEROPS peptidase family G6.	Domain
C, D	PF00071	Ras family (Ras)	Ras family	Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See Pfam:PF00009 Pfam:PF00025, Pfam:PF00063. As regards Rab GTPases, these are important regulators of vesicle formation, motil ...	Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See Pfam:PF00009 Pfam:PF00025, Pfam:PF00063. As regards Rab GTPases, these are important regulators of vesicle formation, motility and fusion. They share a fold in common with all Ras GTPases: this is a six-stranded beta-sheet surrounded by five alpha-helices [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth B], B [auth A]	Toxin B	glycosyltransferase activity transferase activity catalytic activity binding lipid binding toxin activity cysteine-type peptidase activity peptidase activity catalytic activity, acting on a protein hydrolase activity cation binding ion binding metal ion binding small molecule binding	proteolysis metabolic process cellular process primary metabolic process protein metabolic process macromolecule metabolic process	cellular anatomical structure membrane extracellular region host intracellular membrane-bounded organelle host cellular component host intracellular part host cell membrane host cell cytoplasm part host intracellular organelle host cell endosome membrane host cell cytoplasm host cell part host cell endosome host intracellular region cellular anatomical structure membrane extracellular region host intracellular membrane-bounded organelle host cellular component host intracellular part host cell membrane host cell cytoplasm part host intracellular organelle host cell endosome membrane host cell cytoplasm host cell part host cell endosome host intracellular region host cell plasma membrane host cell cytosol
C, D	Ras-related protein R-Ras	guanyl nucleotide binding binding nucleotide binding GDP binding guanyl ribonucleotide binding purine ribonucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding guanyl nucleotide binding binding nucleotide binding GDP binding guanyl ribonucleotide binding purine ribonucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding protein-containing complex binding GTP binding purine ribonucleoside triphosphate binding pyrophosphatase activity GTPase activity ribonucleoside triphosphate phosphatase activity hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides hydrolase activity hydrolase activity, acting on acid anhydrides catalytic activity	developmental process multicellular organismal process cellular developmental process glial cell migration nervous system development Schwann cell migration neurogenesis multicellular organism development gliogenesis cell differentiation anatomical structure development cellular process cell migration cell motility developmental process multicellular organismal process cellular developmental process glial cell migration nervous system development Schwann cell migration neurogenesis multicellular organism development gliogenesis cell differentiation anatomical structure development cellular process cell migration cell motility system development hemopoiesis cell development leukocyte differentiation positive regulation of locomotion regulation of biological process regulation of cell motility regulation of cellular process endothelial cell migration biological regulation positive regulation of biological process positive regulation of cell migration regulation of locomotion positive regulation of endothelial cell migration positive regulation of cell motility regulation of cell migration regulation of endothelial cell migration locomotion positive regulation of cellular process regulation of developmental process angiogenesis regulation of vasculature development positive regulation of developmental process tube morphogenesis regulation of multicellular organismal process regulation of anatomical structure morphogenesis blood vessel development regulation of multicellular organismal development blood vessel morphogenesis tube development positive regulation of angiogenesis vasculature development circulatory system development anatomical structure morphogenesis positive regulation of vasculature development regulation of angiogenesis anatomical structure formation involved in morphogenesis positive regulation of multicellular organismal process negative regulation of locomotion negative regulation of glial cell migration negative regulation of Schwann cell migration negative regulation of biological process regulation of glial cell migration regulation of Schwann cell migration negative regulation of cellular process negative regulation of cell migration negative regulation of cell motility cellular response to stimulus regulation of signaling response to stimulus signaling regulation of signal transduction regulation of MAPK cascade intracellular signal transduction cell communication regulation of intracellular signal transduction regulation of response to stimulus intracellular signaling cassette MAPK cascade regulation of cell communication ERK1 and ERK2 cascade signal transduction regulation of ERK1 and ERK2 cascade head development face morphogenesis head morphogenesis face development body morphogenesis regulation of vasculogenesis regulation of cell differentiation vasculogenesis positive regulation of cell differentiation positive regulation of vasculogenesis endothelial cell-matrix adhesion regulation of cell-substrate adhesion positive regulation of cell adhesion regulation of cell adhesion cell-substrate adhesion positive regulation of cell-matrix adhesion positive regulation of endothelial cell-matrix adhesion via fibronectin cell adhesion regulation of endothelial cell-matrix adhesion via fibronectin cell-matrix adhesion positive regulation of cell-substrate adhesion regulation of cell-matrix adhesion endothelial cell-matrix adhesion via fibronectin regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction phosphatidylinositol 3-kinase/protein kinase B signal transduction small GTPase-mediated signal transduction Ras protein signal transduction	cellular anatomical structure anchoring junction cell junction focal adhesion cell-substrate junction extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cellular anatomical structure anchoring junction cell junction focal adhesion cell-substrate junction extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell periphery plasma membrane membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A [auth B], B [auth A]	IPR038383	CGT/MARTX, cysteine protease (CPD) domain superfamily	Homologous Superfamily
A [auth B], B [auth A]	IPR024772	TcdA/TcdB toxin, N-terminal helical domain	Domain
A [auth B], B [auth A]	IPR020974	CGT/MARTX, cysteine protease (CPD) domain	Domain
A [auth B], B [auth A]	IPR024769	TcdA/TcdB toxin, pore forming domain	Domain
A [auth B], B [auth A]	IPR029044	Nucleotide-diphospho-sugar transferases	Homologous Superfamily
A [auth B], B [auth A]	IPR020972	Dermonecrotic/RTX toxin, membrane localization domain	Domain
A [auth B], B [auth A]	IPR024770	TcdA/TcdB toxin, catalytic glycosyltransferase domain	Domain
A [auth B], B [auth A]	IPR018337	Cell wall/choline-binding repeat	Repeat
C, D	IPR005225	Small GTP-binding domain	Domain
C, D	IPR020849	Small GTPase, Ras-type	Family
C, D	IPR001806	Small GTPase	Family
C, D	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
C, D	Pharos: P10301	juvenile myelomonocytic leukemia Noonan syndrome prostate cancer rheumatoid arthritis systemic sclerosis vitiligo breast carcinoma glioblastoma hypothyroidism lung adenocarcinoma malignant pancreatic neoplasm skin basal cell carcinoma tuberculosis breast fibroadenoma Hashimoto thyroiditis juvenile myelomonocytic leukemia Noonan syndrome prostate cancer rheumatoid arthritis systemic sclerosis vitiligo breast carcinoma glioblastoma hypothyroidism lung adenocarcinoma malignant pancreatic neoplasm skin basal cell carcinoma tuberculosis breast fibroadenoma Hashimoto thyroiditis invasive ductal breast carcinoma lung carcinoma myositis ovarian cancer Prostatic Neoplasms systemic lupus erythematosus ulcerative colitis ductal breast carcinoma in situ Hodgkins lymphoma malignant glioma non-small cell lung carcinoma pancreatic ductal adenocarcinoma

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.