PDBsum entry 2bov

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
Protein chains
174 a.a. *
208 a.a. *
Waters ×261
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Molecular recognition of an adp-ribosylating clostridium botulinum c3 exoenzyme by rala gtpase
Structure: Ras-related protein ral-a. Chain: a. Synonym: rala. Engineered: yes. Mono-adp-ribosyltransferase c3. Chain: b. Synonym: c3bot1 exoenzyme, exoenzyme c3. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Clostridium botulinum. Organism_taxid: 1491.
2.66Å     R-factor:   0.206     R-free:   0.274
Authors: K.P.Holbourn,J.M.Sutton,H.R.Evans,C.C.Shone,K.R.Acharya
Key ref:
K.P.Holbourn et al. (2005). Molecular recognition of an ADP-ribosylating Clostridium botulinum C3 exoenzyme by RalA GTPase. Proc Natl Acad Sci U S A, 102, 5357-5362. PubMed id: 15809419 DOI: 10.1073/pnas.0501525102
14-Apr-05     Release date:   15-Apr-05    
Supersedes: 1wca
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P11233  (RALA_HUMAN) -  Ras-related protein Ral-A
206 a.a.
174 a.a.
Protein chain
Pfam   ArchSchema ?
P15879  (ARC3_CBDP) -  Mono-ADP-ribosyltransferase C3
251 a.a.
208 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   11 terms 
  Biological process     metabolic process   21 terms 
  Biochemical function     nucleotide binding     10 terms  


DOI no: 10.1073/pnas.0501525102 Proc Natl Acad Sci U S A 102:5357-5362 (2005)
PubMed id: 15809419  
Molecular recognition of an ADP-ribosylating Clostridium botulinum C3 exoenzyme by RalA GTPase.
K.P.Holbourn, J.M.Sutton, H.R.Evans, C.C.Shone, K.R.Acharya.
C3 exoenzymes (members of the ADP-ribosyltranferase family) are produced by Clostridium botulinum (C3bot1 and -2), Clostridium limosum (C3lim), Bacillus cereus (C3cer), and Staphylococcus aureus (C3stau1-3). These exoenzymes lack a translocation domain but are known to specifically inactivate Rho GTPases in host target cells. Here, we report the crystal structure of C3bot1 in complex with RalA (a GTPase of the Ras subfamily) and GDP at a resolution of 2.66 A. RalA is not ADP-ribosylated by C3 exoenzymes but inhibits ADP-ribosylation of RhoA by C3bot1, C3lim, and C3cer to different extents. The structure provides an insight into the molecular interactions between C3bot1 and RalA involving the catalytic ADP-ribosylating turn-turn (ARTT) loop from C3bot1 and helix alpha4 and strand beta6 (which are not part of the GDP-binding pocket) from RalA. The structure also suggests a molecular explanation for the different levels of C3-exoenzyme inhibition by RalA and why RhoA does not bind C3bot1 in this manner.
  Selected figure(s)  
Figure 2.
Fig. 2. The C3bot1-RalA interface and ARTT loop. (A) Close-up stereoview of the interface between C3bot1 (red and blue) and RalA (yellow) with two water molecules (turquoise). The dashed lines represent hydrogen bonds. (B) Superposition of the ARTT loop from the native C3bot1 structure (gray) and the complex (yellow).
Figure 3.
Fig. 3. Comparison of the interface regions for the C3 exoenzymes and the Rho and Ras GTPases. (A) Sequence alignment performed by T-COFFEE (43) of the related C3 exoenzymes, colored by similarity, with orange being the most similar and green the least similar. The sequences are numbered starting at the first residue of the mature protein, with the exception of C3bot1, which is numbered like the crystal structures (24-26). The residue to which the number applies is the one under the first digit. The conserved residues within the ARTT loop (207-214) are highlighted in turquoise. The seven residues that interact (through H-bond) with RalA (K56, Y63, K73, K81, D204, P205, and S207) are shaded in gray. (B) Detailed stereoview of the C3bot1 (gold) RalA-binding region illustrating all the residues involved in the binding and their equivalent residues in the overlaid C3stau2 (silver). (C) Sequence alignment performed by T-COFFEE (43) of the related GTPases, colored by similarity and numbered as in A. The sequences are all numbered from the first residue of the protein. The residues that interact (through H-bond) with C3bot1 (highlighted in red) are S129, E132, E140, K143, E147, and E155.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19824793 M.R.Popoff, and P.Bouvet (2009).
Clostridial toxins.
  Future Microbiol, 4, 1021-1064.  
17955301 H.Namazi (2008).
Practice pearl: a novel use of botulinum toxin for unicameral bone cyst ablation.
  Ann Surg Oncol, 15, 657-658.  
18043972 H.Namazi (2008).
A novel use of botulinum toxin to ameliorate bone cancer pain.
  Ann Surg Oncol, 15, 1259-1260.  
18165877 H.Namazi (2008).
Botulinum toxin: a novel adjuvant for giant cell tumor.
  Ann Surg Oncol, 15, 2066-2067.  
18299799 H.Namazi (2008).
Botulinum toxin type-A therapy in cluster headache: a novel molecular mechanism.
  J Headache Pain, 9, 133.  
17146673 M.Vogelsgesang, A.Pautsch, and K.Aktories (2007).
C3 exoenzymes, novel insights into structure and action of Rho-ADP-ribosylating toxins.
  Naunyn Schmiedebergs Arch Pharmacol, 374, 347-360.  
16493654 P.Radivojac, S.Vucetic, T.R.O'Connor, V.N.Uversky, Z.Obradovic, and A.K.Dunker (2006).
Calmodulin signaling: analysis and prediction of a disorder-dependent molecular recognition.
  Proteins, 63, 398-410.  
16177825 A.Pautsch, M.Vogelsgesang, J.Tränkle, C.Herrmann, and K.Aktories (2005).
Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme.
  EMBO J, 24, 3670-3680.
PDB codes: 2a78 2a9k
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