 |
PDBsum entry 3b8h
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Biosynthetic protein/transferase
|
PDB id
|
|
|
|
3b8h
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
The nature and character of the transition state for the ADP-Ribosyltransferase reaction.
|
|
|
Authors
|
|
R.Jørgensen,
Y.Wang,
D.Visschedyk,
A.R.Merrill.
|
|
|
Ref.
|
|
Embo Rep, 2008,
9,
802-809.
|
|
|
PubMed id
|
|
|
|
|
Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
|
|
|
|
Abstract
|
|
|
Exotoxin A (ExoA) from Pseudomonas aeruginosa is an important virulence factor
that belongs to a class of exotoxins that are secreted by pathogenic bacteria
which cause human diseases such as cholera, diphtheria, pneumonia and whooping
cough. We present the first crystal structures, to our knowledge, of ExoA in
complex with elongation factor 2 (eEF2) and intact NAD(+), which indicate a
direct role of two active-site loops in ExoA during the catalytic cycle. One
loop moves to form a solvent cover for the active site of the enzyme and reaches
towards the target residue (diphthamide) in eEF2 forming an important hydrogen
bond. The NAD(+) substrate adopts a conformation remarkably different from that
of the NAD(+) analogue, betaTAD, observed in previous structures, and fails to
trigger any loop movements. Mutational studies of the two loops in the toxin
identify several residues important for catalytic activity, in particular Glu
546 and Arg 551, clearly supporting the new complex structures. On the basis of
these data, we propose a transition-state model for the toxin-catalysed reaction.
|
|
|
|
|
|
|
