Oxaloacetate
Family: Asparagine (N)
General features
R group: -CH2-C(NH2)O
MW: 132.12 g mol-1
pKa of R group: NA
Physiological roles
Glycosylation:
Personal annotation of figure from the abstract of
Larkin, Imeriali (2011)
Within the past decade it has been confirmed that
eukaryotes are not the only domain that will link glycans to large proteins
during their processing in the lumen of the ER. Gram negative species have been
found to bind glycan (polysaccharide groups) to proteins in the periplasm. The
polysaccharide is elongated on the cytoplasmic side of the cell membrane while
anchored to the cell membrane via Und-PP. When finished, the
Und-PP-polysaccharide is translocated to the outer leaflet to face the
periplasm where it can be linked to finished protein via an asparagines residue
on that protein.
http://pubs.acs.org/doi/abs/10.1021/bi200346n
This process is very similar to peptidoglycan and
LPS synthesis.
Interesting to note, is that in the context of
translation, tRNAAsn is initially loaded with aspartate, and
subsequently the carboxyl group is changed by an amidotransferase (this is also
the case with tRNAGln). In this many bacteria lack an Asn tRNA synthetase
but use a Asp tRNA synthetase that has amidotransferase activitiy. This is thought to be a potentially
mechanism for future antibiotics; this mode of interference with protein
synthesis has already been implemented in cancer chemotherapy treatments. Just
like with cancer chemotherapy, there is limitation to the selective toxicity of
this method, because mitochondrial-directed translation also uses this modified
Asn/Gln tRNA charging method. For more info, one of the situation is described
in the in the introduction to this article: http://nar.oxfordjournals.org/content/early/2012/02/22/nar.gks167.full It was also described in this review
article: doi: 10.1101/gad.1187404
Genes
& Dev. 2004. 18: 731-738 Also,
the characterization of the ribozyme that generates this ‘different’ Asn-tRNA
can be read in this paper: http://www.ncbi.nlm.nih.gov/pubmed/18241796
Synthesis
Two enzymes (from independent genes) are known to
synthesize asparagine in bacteria: AsnA , which catalyzes the reaction referred to as
“ammonia-dependent” and can only use ammonia as the nitrogen source to convert
aspartic acid to asparagines, and AsnB, whose reaction is referred to as
“glutamine-dependent” can use either ammonia or glutamine as the nitrogen donor
(often glutamine). AsnB has
amidotransferase activity (meaning it transfers the transfer of the amide group
of one amino acid to another.) The AsnA pathway is found only in prokaryotes
while the AsnB pathway exists in eukaryotes as well as prokaryotes. Because of
that fact, and the efficacy of cancer chemotherapeutics effective in the AsnB
directed pathway, this enzyme/pathway is better studied than that of AsnA.
Ammonia-dependent
(AsnA):
ATP +
L-aspartate + NH3 = AMP + diphosphate + L-asparagine
Glutamine-dependent
(AsnB):
ATP +
L-aspartate + L-glutamine + H2O = AMP + diphosphate + L-asparagine +
L-glutamate
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