 |
PDBsum entry 2jb4
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Oxidoreductase
|
PDB id
|
|
|
|
2jb4
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
A cyclobutanone analogue mimics penicillin in binding to isopenicillin n synthase.
|
|
|
Authors
|
|
A.C.Stewart,
I.J.Clifton,
R.M.Adlington,
J.E.Baldwin,
P.J.Rutledge.
|
|
|
Ref.
|
|
Chembiochem, 2007,
8,
2003-2007.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
A carbocyclic analogue of the beta-lactam antibiotic isopenicillin N (IPN) has
been synthesised and cocrystallised with isopenicillin N synthase (IPNS), the
central enzyme in the biosynthesis of penicillin antibiotics. The crystal
structure of the IPNS-cyclobutanone complex reveals an active site environment
similar to that seen in the enzyme-product complex generated by turnover of the
natural substrate within the crystalline protein. The IPNS-cyclobutanone
structure demonstrates that the product analogue is tethered to the protein by
hydrogen bonding and salt bridge interactions with its carboxylate groups, as
seen previously for the natural substrate and product. Furthermore, the
successful cocrystallisation of this analogue with IPNS provides firm structural
evidence for the utility of such cyclobutanone derivatives as hydrolytically
stable analogues of bicyclic beta-lactams.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
The reaction cycle of isopenicillin n synthase observed by X-Ray diffraction.
|
|
|
Authors
|
|
N.I.Burzlaff,
P.J.Rutledge,
I.J.Clifton,
C.M.Hensgens,
M.Pickford,
R.M.Adlington,
P.L.Roach,
J.E.Baldwin.
|
|
|
Ref.
|
|
Nature, 1999,
401,
721-724.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Figure 2.
Figure 2 Proposed mechanisms for the oxidation of ACV and
ACmC to bicyclic and monocyclic products, respectively. See text
for details of compounds 1-6. AA, L-  -(
 -aminoadipoyl).
|
|
Figure 3.
Figure 3 Stereo views of the two substrates and two products
overlaid. The key regions that participate in the reaction and
the iron atom (orange) are shown; the aminoadipoyl side chain,
which does not move significantly, is omitted for clarity. Shown
are ACV (white), IPN (yellow), ACmC (blue) and its monocyclic
sulphoxide product (pink). Figures were prepared using the
programs MOLSCRIPT20 and Raster3D (ref. 21).
|
|
|
|
|
|
The above figures are
reproduced from the cited reference
with permission from Macmillan Publishers Ltd
|
|
|
|
|
|
|
