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Literature summary for 2.7.8.35 extracted from

  • Mitachi, K.; Siricilla, S.; Yang, D.; Kong, Y.; Skorupinska-Tudek, K.; Swiezewska, E.; Franzblau, S.G.; Kurosu, M.
    Fluorescence-based assay for polyprenyl phosphate-GlcNAc-1-phosphate transferase (WecA) and identification of novel antimycobacterial WecA inhibitors (2016), Anal. Biochem., 512, 78-90.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development the enzyme is a target for development of drugs Mycobacterium tuberculosis

Cloned(Commentary)

Cloned (Comment) Organism
gene wecA, recombinant overexpression in Escherichia coli strain BL21 Escherichia coli

Inhibitors

Inhibitors Comment Organism Structure
DMSO 50% inhibition at 10% v/v, no inhibition at 2.86% v/v Escherichia coli
DMSO 50% inhibition at 10% v/v, no inhibition at 2.86% v/v Mycolicibacterium smegmatis
additional information synthesis and evaluation of a series of capuramycin analogues as WecA enzyme inhibitors. No inhibition by capuramycin, UT-01309, and SQ641 Escherichia coli
additional information synthesis and evaluation of a series of capuramycin analogues as WecA enzyme inhibitors. No inhibition by capuramycin, UT-01309, and SQ641 Mycolicibacterium smegmatis
tunicamycin complete inhibition at 0.02 mg/ml, 36% at 20 ng/ml Escherichia coli
tunicamycin
-
Mycobacterium tuberculosis
tunicamycin
-
Mycolicibacterium smegmatis
UT-01320 complete inhibition at 0.02 mg/ml, 42% at 20 ng/ml Escherichia coli
UT-01320 a selective WecA inhibitor that kills both replicating and non-replicating Mycobacterium tuberculosis cells at 0.0015-0.00258 mg/ml , respectively Mycobacterium tuberculosis
UT-01320
-
Mycolicibacterium smegmatis
UT-03325 55% inhibition at 0.02 mg/ml, 30% at 20 ng/ml Escherichia coli
UT-03325
-
Mycolicibacterium smegmatis
UT-03328 60.5% inhibition at 0.02 mg/ml, no inhibition at 20 ng/ml Escherichia coli
UT-03328
-
Mycolicibacterium smegmatis
UT-03347 80.5% inhibition at 0.02 mg/ml, 11% at 20 ng/ml Escherichia coli
UT-03347
-
Mycolicibacterium smegmatis

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information Michaelis-Menten enzyme kinetics Escherichia coli
additional information
-
additional information Michaelis-Menten enzyme kinetics Mycobacterium tuberculosis
additional information
-
additional information Michaelis-Menten enzyme kinetics Mycolicibacterium smegmatis

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Escherichia coli
Mg2+ required Mycobacterium tuberculosis
Mg2+ required Mycolicibacterium smegmatis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
UDP-N-acetyl-alpha-D-glucosamine + trans,octacis-decaprenyl phosphate Escherichia coli
-
UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-trans,octacis-decaprenol
-
?
UDP-N-acetyl-alpha-D-glucosamine + trans,octacis-decaprenyl phosphate Mycobacterium tuberculosis
-
UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-trans,octacis-decaprenol
-
?
UDP-N-acetyl-alpha-D-glucosamine + trans,octacis-decaprenyl phosphate Mycolicibacterium smegmatis
-
UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-trans,octacis-decaprenol
-
?
UDP-N-acetyl-alpha-D-glucosamine + trans,octacis-decaprenyl phosphate Mycolicibacterium smegmatis mc(2)155 / ATCC 700084
-
UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-trans,octacis-decaprenol
-
?
UDP-N-acetyl-alpha-D-glucosamine + trans,octacis-decaprenyl phosphate Mycobacterium tuberculosis H37Rv
-
UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-trans,octacis-decaprenol
-
?

Organism

Organism UniProt Comment Textmining
Escherichia coli P0AC78 gene wecA
-
Mycobacterium tuberculosis P9WMW5 gene wecA
-
Mycobacterium tuberculosis H37Rv P9WMW5 gene wecA
-
Mycolicibacterium smegmatis A0R211 gene wecA
-
Mycolicibacterium smegmatis mc(2)155 / ATCC 700084 A0R211 gene wecA
-

Purification (Commentary)

Purification (Comment) Organism
preparation of membrane fraction Mycobacterium tuberculosis
preparation of membrane fraction Mycolicibacterium smegmatis

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information specificity of WecA against truncated prenyl phosphates, overview Mycobacterium tuberculosis ?
-
?
additional information specificity of WecA against truncated prenyl phosphates, overview. Decaprenyl phosphate and undecaprenyl phosphate are equally effective, no activity with substrates that have shorter prenyl chains Escherichia coli ?
-
?
additional information specificity of WecA against truncated prenyl phosphates, overview. Decaprenyl phosphate and undecaprenyl phosphate are equally effective, no activity with substrates that have shorter prenyl chains Mycolicibacterium smegmatis ?
-
?
additional information specificity of WecA against truncated prenyl phosphates, overview. Decaprenyl phosphate and undecaprenyl phosphate are equally effective, no activity with substrates that have shorter prenyl chains Mycolicibacterium smegmatis mc(2)155 / ATCC 700084 ?
-
?
additional information specificity of WecA against truncated prenyl phosphates, overview Mycobacterium tuberculosis H37Rv ?
-
?
UDP-N-acetyl-alpha-D-glucosamine + trans,octacis-decaprenyl phosphate
-
Escherichia coli UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-trans,octacis-decaprenol
-
?
UDP-N-acetyl-alpha-D-glucosamine + trans,octacis-decaprenyl phosphate
-
Mycobacterium tuberculosis UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-trans,octacis-decaprenol
-
?
UDP-N-acetyl-alpha-D-glucosamine + trans,octacis-decaprenyl phosphate
-
Mycolicibacterium smegmatis UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-trans,octacis-decaprenol
-
?
UDP-N-acetyl-alpha-D-glucosamine + trans,octacis-decaprenyl phosphate
-
Mycolicibacterium smegmatis mc(2)155 / ATCC 700084 UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-trans,octacis-decaprenol
-
?
UDP-N-acetyl-alpha-D-glucosamine + trans,octacis-decaprenyl phosphate
-
Mycobacterium tuberculosis H37Rv UMP + N-acetyl-alpha-D-glucosaminyl-diphospho-trans,octacis-decaprenol
-
?

Synonyms

Synonyms Comment Organism
polyprenyl phosphate-GlcNAc-1-phosphate transferase
-
Escherichia coli
polyprenyl phosphate-GlcNAc-1-phosphate transferase
-
Mycobacterium tuberculosis
polyprenyl phosphate-GlcNAc-1-phosphate transferase
-
Mycolicibacterium smegmatis
WecA
-
Escherichia coli
WecA
-
Mycobacterium tuberculosis
WecA
-
Mycolicibacterium smegmatis

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Escherichia coli
37
-
assay at Mycobacterium tuberculosis
37
-
assay at Mycolicibacterium smegmatis

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
assay at Escherichia coli
8
-
assay at Mycobacterium tuberculosis
8
-
assay at Mycolicibacterium smegmatis

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
additional information
-
IC50 for tunicamycin is 120 ng/ml at pH 8.0 37°C Escherichia coli additional information
additional information
-
IC50 for tunicamycin is 590 ng/ml at pH 8.0 37°C Mycolicibacterium smegmatis additional information

General Information

General Information Comment Organism
malfunction inhibition of WecA will block the entire biosynthesis of essential cell wall components of Mtb in both replicating and non-replicating states Mycobacterium tuberculosis
physiological function WecA catalyzes the transformation from UDP-N-acetyl-alpha-D-glucosamine to N-acetyl-alpha-D-glucosaminyl-diphospho-trans,octacis-decaprenol the first membrane-anchored glycophospholipid that is responsible for the biosynthesis of mycolylarabinogalactan Mycobacterium tuberculosis