Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • Ishizaki, Y.; Hayashi, C.; Inoue, K.; Igarashi, M.; Takahashi, Y.; Pujari, V.; Crick, D.C.; Brennan, P.J.; Nomoto, A.
    Inhibition of the first step in synthesis of the mycobacterial cell wall core, catalyzed by the GlcNAc-1-phosphate transferase WecA, by the novel caprazamycin derivative CPZEN-45 (2013), J. Biol. Chem., 288, 30309-30319.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.7.8.35 drug development enzyme WecA is a promising target for the development of antituberculous drugs as a countermeasure of drug resistant tuberculosis Mycobacterium tuberculosis

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.8.35 gene wecA, recombinant expression in Mycobacterium smegmatis strain 8a10 Mycobacterium tuberculosis

Protein Variants

EC Number Protein Variants Comment Organism
2.7.8.33 T728G naturally occuring mutation in TagO leading to CPZEN-45 resistance Bacillus subtilis

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.8.13 caprazamycin B
-
 Bacillus subtilis
2.7.8.13 CPZEN-45 CPZEN-45 strongly inhibits incorporation of radiolabeled glycerol into growing cultures and shows antibacterial activity against caprazamycin-resistant strains, including a strain overexpressing translocase-I MraY, involved in the biosynthesis of peptidoglycan, the target of the caprazamycins. Very poor inhibition by vancomycin Bacillus subtilis
2.7.8.13 tunicamycin
-
 Bacillus subtilis
2.7.8.33 caprazamycin B
-
 Bacillus subtilis
2.7.8.33 CPZEN-45 the primary target of CPZEN-45 in Bacillus subtilis is TagO, which is a different target from that of the parent caprazamycins. CPZEN-45 is not effective against a strain overexpressing undecaprenyl-phosphate-GlcNAc-1-phosphate transferase (TagO, involved in the biosynthesis of teichoic acid) due to a mutation T728G in the tagO gene ir responsible for the spontaneous CPZEN-45-resistant strain. Very poor inhibition by vancomycin Bacillus subtilis
2.7.8.33 tunicamycin
-
 Bacillus subtilis
2.7.8.35 CPZEN-45 a caprazamycin derivative, CPZEN-45 shows excellent antitubercular activity against not only drug-sensitive strains but also some multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis strains Mycobacterium tuberculosis
2.7.8.35 additional information poor inhibition by caprazamycin B Mycobacterium tuberculosis
2.7.8.35 tunicamycin
-
 Mycobacterium tuberculosis
2.7.8.35 Vancomycin weak inhibition Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.8.13 UDP-N-acetyl-alpha-D-glucosamine + ditrans,octacis-undecaprenyl phosphate Bacillus subtilis
-
 UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol
-
 ?
2.7.8.13 UDP-N-acetyl-alpha-D-glucosamine + ditrans,octacis-undecaprenyl phosphate Bacillus subtilis 168
-
 UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol
-
 ?
2.7.8.33 UDP-N-acetyl-alpha-D-glucosamine + ditrans,octacis-undecaprenyl phosphate Bacillus subtilis
-
 UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol
-
 ?
2.7.8.33 UDP-N-acetyl-alpha-D-glucosamine + ditrans,octacis-undecaprenyl phosphate Bacillus subtilis 168
-
 UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.8.13 Bacillus subtilis Q03521 gene mraY
-
2.7.8.13 Bacillus subtilis 168 Q03521 gene mraY
-
2.7.8.33 Bacillus subtilis O34753 TagO; gene tagO
-
2.7.8.33 Bacillus subtilis 168 O34753 TagO; gene tagO
-
2.7.8.35 Mycobacterium tuberculosis P9WMW5 gene wecA or Rv1302 or Rfe
-
2.7.8.35 Mycobacterium tuberculosis H37Rv P9WMW5 gene wecA or Rv1302 or Rfe
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.8.13 UDP-N-acetyl-alpha-D-glucosamine + ditrans,octacis-undecaprenyl phosphate
-
 Bacillus subtilis UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol
-
 ?
2.7.8.13 UDP-N-acetyl-alpha-D-glucosamine + ditrans,octacis-undecaprenyl phosphate
-
 Bacillus subtilis 168 UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol
-
 ?
2.7.8.33 UDP-N-acetyl-alpha-D-glucosamine + ditrans,octacis-undecaprenyl phosphate
-
 Bacillus subtilis UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol
-
 ?
2.7.8.33 UDP-N-acetyl-alpha-D-glucosamine + ditrans,octacis-undecaprenyl phosphate
-
 Bacillus subtilis 168 UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.8.13 MraY
-
 Bacillus subtilis
2.7.8.13 translocase-I
-
 Bacillus subtilis
2.7.8.33 TagO
-
 Bacillus subtilis
2.7.8.33 undecaprenyl-phosphate-GlcNAc-1-phosphate transferase
-
 Bacillus subtilis
2.7.8.35 decaprenyl-phosphate N-acetylglucosaminephosphotransferase UniProt Mycobacterium tuberculosis
2.7.8.35 GlcNAc-1-phosphate transferase
-
 Mycobacterium tuberculosis
2.7.8.35 WecA
-
 Mycobacterium tuberculosis

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.7.8.13 0.00005
-
 pH and temperature not specified in the publication Bacillus subtilis caprazamycin B
2.7.8.13 0.0004
-
 pH and temperature not specified in the publication Bacillus subtilis CPZEN-45
2.7.8.33 0.00005
-
 pH and temperature not specified in the publication Bacillus subtilis CPZEN-45
2.7.8.33 0.00015
-
 pH and temperature not specified in the publication Bacillus subtilis caprazamycin B
2.7.8.35 0.00004
-
 pH and temperature not specified in the publication Mycobacterium tuberculosis CPZEN-45
2.7.8.35 0.004
-
 pH and temperature not specified in the publication Mycobacterium tuberculosis Vancomycin

General Information

EC Number General Information Comment Organism
2.7.8.13 metabolism the enzyme is involved in the biosynthesis of peptidoglycan Bacillus subtilis
2.7.8.33 metabolism the enzyme is involved in the biosynthetic pathway of peptidoglycan and teichoic acid in Bacillus subtilis strain 168, overview Bacillus subtilis
2.7.8.35 metabolism the enzyme is involved in the biosynthesis of the mycolylarabinogalactan of the cell wall of Mycobacterium tuberculosis Mycobacterium tuberculosis