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PDBsum entry 1xk9

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1xk9
Jmol
Contents
Protein chains
204 a.a.
Ligands
P34 ×2
Waters ×401
PDB id:
1xk9
Name: Transferase
Title: Pseudomanas exotoxin a in complex with the pj34 inhibitor
Structure: Exotoxin a. Chain: a, b. Fragment: catalytic fragment, pe24h. Synonym: NAD-dependent adp-ribosyltransferase. Engineered: yes
Source: Pseudomonas aeruginosa. Organism_taxid: 287. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.10Å     R-factor:   0.213     R-free:   0.235
Authors: S.P.Yates,P.J.Taylor,R.Joergensen,D.Ferrraris,J.Zhang, G.R.Andersen,A.R.Merrill
Key ref: S.P.Yates et al. (2005). Structure-function analysis of water-soluble inhibitors of the catalytic domain of exotoxin A from Pseudomonas aeruginosa. Biochem J, 385, 667-675. PubMed id: 15458385 DOI: 10.1042/BJ20041480
Date:
28-Sep-04     Release date:   17-May-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P11439  (TOXA_PSEAE) -  Exotoxin A
Seq:
Struc:
 
Seq:
Struc:
638 a.a.
204 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.2.4.2.36  - NAD(+)--diphthamide ADP-ribosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: NAD+ + diphthamide-[translation elongation factor 2] = nicotinamide + N-(ADP-D-ribosyl)diphthamide-[translation elongation factor 2]
NAD(+)
+ diphthamide-[translation elongation factor 2]
= nicotinamide
+ N-(ADP-D-ribosyl)diphthamide-[translation elongation factor 2]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     NAD+-diphthamide ADP-ribosyltransferase activity     1 term  

 

 
    Added reference    
 
 
DOI no: 10.1042/BJ20041480 Biochem J 385:667-675 (2005)
PubMed id: 15458385  
 
 
Structure-function analysis of water-soluble inhibitors of the catalytic domain of exotoxin A from Pseudomonas aeruginosa.
S.P.Yates, P.L.Taylor, R.Jørgensen, D.Ferraris, J.Zhang, G.R.Andersen, A.R.Merrill.
 
  ABSTRACT  
 
The mono-ADPRT (mono-ADP-ribosyltransferase), Pseudomonas aeruginosa ETA (exotoxin A), catalyses the transfer of ADP-ribose from NAD+ to its protein substrate. A series of water-soluble compounds that structurally mimic the nicotinamide moiety of NAD+ was investigated for their inhibition of the catalytic domain of ETA. The importance of an amide locked into a hetero-ring structure and a core hetero-ring system that is planar was a trend evident by the IC50 values. Also, the weaker inhibitors have core ring structures that are less planar and thus more flexible. One of the most potent inhibitors, PJ34, was further characterized and shown to exhibit competitive inhibition with an inhibition constant K(i) of 140 nM. We also report the crystal structure of the catalytic domain of ETA in complex with PJ34, the first example of a mono-ADPRT in complex with an inhibitor. The 2.1 A (1 A=0.1 nm) resolution structure revealed that PJ34 is bound within the nicotinamide-binding pocket and forms stabilizing hydrogen bonds with the main chain of Gly-441 and to the side-chain oxygen of Gln-485, a member of a proposed catalytic loop. Structural comparison of this inhibitor complex with diphtheria toxin (a mono-ADPRT) and with PARPs [poly(ADP-ribose) polymerases] shows similarity of the catalytic residues; however, a loop similar to that found in ETA is present in diphtheria toxin but not in PARP. The present study provides insight into the important features required for inhibitors that mimic NAD+ and their binding to the mono-ADPRT family of toxins.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21219649 D.Lee, T.A.de Beer, R.A.Laskowski, J.M.Thornton, and C.A.Orengo (2011).
1,000 structures and more from the MCSG.
  BMC Struct Biol, 11, 2.  
19360129 J.E.Grotzke, M.J.Harriff, A.C.Siler, D.Nolt, J.Delepine, D.A.Lewinsohn, and D.M.Lewinsohn (2009).
The Mycobacterium tuberculosis phagosome is a HLA-I processing competent organelle.
  PLoS Pathog, 5, e1000374.  
18454192 A.Arnoldo, J.Curak, S.Kittanakom, I.Chevelev, V.T.Lee, M.Sahebol-Amri, B.Koscik, L.Ljuma, P.J.Roy, A.Bedalov, G.Giaever, C.Nislow, R.A.Merrill, S.Lory, and I.Stagljar (2008).
Identification of small molecule inhibitors of Pseudomonas aeruginosa exoenzyme S using a yeast phenotypic screen.
  PLoS Genet, 4, e1000005.  
18276581 R.Jørgensen, A.E.Purdy, R.J.Fieldhouse, M.S.Kimber, D.H.Bartlett, and A.R.Merrill (2008).
Cholix toxin, a novel ADP-ribosylating factor from Vibrio cholerae.
  J Biol Chem, 283, 10671-10678.
PDB codes: 2q5t 2q6m
18583986 R.Jørgensen, Y.Wang, D.Visschedyk, and A.R.Merrill (2008).
The nature and character of the transition state for the ADP-ribosyltransferase reaction.
  EMBO Rep, 9, 802-809.
PDB codes: 2zit 3b78 3b82 3b8h
16959969 P.O.Hassa, S.S.Haenni, M.Elser, and M.O.Hottiger (2006).
Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going?
  Microbiol Mol Biol Rev, 70, 789-829.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.