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Literature summary for 2.4.2.9 extracted from

  • Villela, A.D.; Pham, H.; Jones, V.; Grzegorzewicz, A.E.; Rodrigues-Junior, V.D.; Campos, M.M.; Basso, L.A.; Jackson, M.; Santos, D.S.
    Analysis of uracil phosphoribosyltransferase expression in Mycobacterium tuberculosis and evaluation of upp knockout strain in infected mice (2017), FEMS Microbiol. Lett., 364, gnx023 .
    View publication on PubMed

Application

Application Comment Organism
additional information MtUPRT is unlikely to be a good target for drugs against Mycobacterium tuberculosis Mycobacterium tuberculosis

Cloned(Commentary)

Cloned (Comment) Organism
gene upp, recombinant expression, the basal level of MtUPRT expression is independent of either growth medium used, addition of bases, or oxygen presence/absence Mycobacterium tuberculosis

Protein Variants

Protein Variants Comment Organism
additional information generation of an upp knockout strain by allelic replacement (using the pPR27xylE plasmid, which contains a thermosensitive origin of replication, the xylE reporter gene and the sacB counterselectable marker), evaluation of it in infected mice. Knockout and complemented strains are validated by a functional assay of uracil incorporation. Recombinant expression of Mycobacterium smegmatis gene upp in Mycobacterium tuberculosis wild-type strain H37Rv, resulting in strain CP, and in the upp knockout (KO) variant of H37Rv. Swiss male mice are infected intravenously with 5 × 105 colony forming units (CFU) of Mycobacterium tuberculosis H37Rv wild-type, knockout, or CP strains Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
additional information MtUPRT is unlikely to be a good target for drugs against Mycobacterium tuberculosis Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
UMP + diphosphate Mycobacterium tuberculosis
-
uracil + 5-phospho-alpha-D-ribose 1-diphosphate
-
?
UMP + diphosphate Mycobacterium tuberculosis H37Rv
-
uracil + 5-phospho-alpha-D-ribose 1-diphosphate
-
?
UMP + diphosphate Mycobacterium tuberculosis ATCC 25618
-
uracil + 5-phospho-alpha-D-ribose 1-diphosphate
-
?

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WFF3
-
-
Mycobacterium tuberculosis ATCC 25618 P9WFF3
-
-
Mycobacterium tuberculosis H37Rv P9WFF3
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
UMP + diphosphate
-
Mycobacterium tuberculosis uracil + 5-phospho-alpha-D-ribose 1-diphosphate
-
?
UMP + diphosphate
-
Mycobacterium tuberculosis H37Rv uracil + 5-phospho-alpha-D-ribose 1-diphosphate
-
?
UMP + diphosphate
-
Mycobacterium tuberculosis ATCC 25618 uracil + 5-phospho-alpha-D-ribose 1-diphosphate
-
?

Synonyms

Synonyms Comment Organism
MtUPRT
-
Mycobacterium tuberculosis
Rv3309c
-
Mycobacterium tuberculosis
UPP
-
Mycobacterium tuberculosis

General Information

General Information Comment Organism
malfunction gene upp disruption does not affect Mycobacterium tuberculosis growth in Middlebrook 7H9 medium, and it is not required for Mycobacterium tuberculosis virulence in a mouse model of infection Mycobacterium tuberculosis
physiological function uracil phosphoribosyltransferase from Mycobacterium tuberculosis (MtUPRT) converts uracil and 5-phosphoribosyl-alpha-1-diphosphate into diphosphate and uridine 5'-monophosphate, the precursor of all pyrimidine nucleotides. Although MtUPRT is a key enzyme of the pyrimidine salvage pathway, as it directly synthetizes UMP from uracil, its levels remain constant under hypoxic conditions. Accordingly, MtUPRT does not appear to play a significant role in the non-replicating latent stage of Mycobacterium tuberculosis in vitro. In addition, the upp gene is not required for the full virulence of Mycobacterium tuberculosis in mice in the model tested. In conclusion, MtUPRT is unlikely to be a good target for anti-tuberculosis drug development Mycobacterium tuberculosis