Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.5.1.4 (
deaminase
)
5,113
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
RidA is a conserved and broadly distributed protein that has enamine
deaminase
activity. In a variety of organisms tested thus far, lack of RidA results in the accumulation of the reactive metabolite 2-aminoacrylate (2AA), an obligate intermediate in the catalytic mechanism of several pyridoxal 5'-phosphate (PLP)-dependent enzymes. This study reports the characterization of variants of the biosynthetic serine/threonine dehydratase (EC 4.3.1.19; IlvA), which is a significant generator of 2AA in the bacteria
Salmonella enterica
,
Escherichia coli
, and
Pseudomonas aeruginosa
and the yeast
Saccharomyces cerevisiae
Two previously identified mutations,
ilvA3210
and
ilvA3211,
suppressed the phenotypic growth consequences of 2AA accumulation in
S. enterica
Characterization of the respective protein variants suggested that they affect 2AA metabolism
in vivo
by two different catalytic mechanisms, both leading to an overall reduction in
serine dehydratase
activity. To emphasize the physiological relevance of the
in vitro
enzyme characterization, we sought to explain
in vivo
phenotypes using these data. A simple mathematical model describing the impact these catalytic deficiencies had on 2AA production was generally supported by our data. However, caveats arose when kinetic parameters, determined
in vitro
, were used to predict formation of the isoleucine precursor 2-ketobutyrate and model
in vivo
(growth) behaviors. Altogether, our data support the need for a holistic approach, including
in vivo
and
in vitro
analyses, to generate data used in understanding and modeling metabolism.
...
PMID:Analyses of variants of the Ser/Thr dehydratase IlvA provide insight into 2-aminoacrylate metabolism in
Salmonella enterica
. 3032 26
