 |
PDBsum entry 1xql
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
E.C.5.1.1.1
- alanine racemase.
|
|
|
|
|
|
|
Reaction:
|
|
L-alanine = D-alanine
|
|
|
|
|
|
L-alanine
Bound ligand (Het Group name = )
matches with 62.50% similarity
|
=
|
D-alanine
|
|
|
|
|
|
|
|
|
|
Cofactor:
|
|
Pyridoxal 5'-phosphate
|
|
|
|
|
|
Pyridoxal 5'-phosphate
Bound ligand (Het Group name =
PMP)
matches with 88.24% similarity
|
|
|
|
|
|
|
Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
| |
|
DOI no:
|
Biochemistry
44:5317-5327
(2005)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Effect of a Y265F mutant on the transamination-based cycloserine inactivation of alanine racemase.
|
|
T.D.Fenn,
T.Holyoak,
G.F.Stamper,
D.Ringe.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
The requirement for d-alanine in the peptidoglycan layer of bacterial cell walls
is fulfilled in part by alanine racemase (EC 5.1.1.1), a pyridoxal 5'-phosphate
(PLP)-assisted enzyme. The enzyme utilizes two antiparallel bases focused at the
C(alpha) position and oriented perpendicular to the PLP ring to facilitate the
equilibration of alanine enantiomers. Understanding how this two-base system is
utilized and controlled to yield reaction specificity is therefore a potential
means for designing antibiotics. Cycloserine is a known alanine racemase suicide
substrate, although its mechanism of inactivation is based on transaminase
chemistry. Here we characterize the effects of a Y265F mutant (Tyr265 acts as
the catalytic base in the l-isomer case) of Bacillus stearothermophilus alanine
racemase on cycloserine inactivation. The Y265F mutant reduces racemization
activity 1600-fold [Watanabe, A., Yoshimura, T., Mikami, B., and Esaki, N.
(1999) J. Biochem. 126, 781-786] and only leads to formation of the isoxazole
end product (the result of the transaminase pathway) in the case of
d-cycloserine, in contrast to results obtained using the wild-type enzyme.
l-Cycloserine, on the other hand, utilizes a number of alternative pathways in
the absence of Y265, emphasizing the importance of Y265 in both the inactivation
and racemization pathway. In combination with the kinetics of inactivation,
these results suggest roles for each of the two catalytic bases in racemization
and inactivation, as well as the importance of Y265 in "steering" the chemistry
to favor one pathway over another.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
J.Lowther,
B.A.Yard,
K.A.Johnson,
L.G.Carter,
V.T.Bhat,
M.C.Raman,
D.J.Clarke,
B.Ramakers,
S.A.McMahon,
J.H.Naismith,
and
D.J.Campopiano
(2010).
Inhibition of the PLP-dependent enzyme serine palmitoyltransferase by cycloserine: evidence for a novel decarboxylative mechanism of inactivation.
|
| |
Mol Biosyst,
6,
1682-1693.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
M.Saito,
G.Chakraborty,
M.Hegde,
J.Ohsie,
S.M.Paik,
C.Vadasz,
and
M.Saito
(2010).
Involvement of ceramide in ethanol-induced apoptotic neurodegeneration in the neonatal mouse brain.
|
| |
J Neurochem,
115,
168-177.
|
|
|
|
|
|
|
H.Barreteau,
A.Kovac,
A.Boniface,
M.Sova,
S.Gobec,
and
D.Blanot
(2008).
Cytoplasmic steps of peptidoglycan biosynthesis.
|
| |
FEMS Microbiol Rev,
32,
168-207.
|
|
|
|
|
|
|
J.Y.Cho
(2007).
Effect of L-cycloserine on cellular responses mediated by macrophages and T cells.
|
| |
Biol Pharm Bull,
30,
2105-2112.
|
|
|
|
|
|
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
code is
shown on the right.
|
|
Links
