Literature summary for 6.3.1.13 extracted from

Patel, K.; Song, F.; Andreana, P.R.
Synthesis of substrate analogues as potential inhibitors for Mycobacterium tuberculosis enzyme MshC (2017), Carbohydr. Res., 453-454, 10-18 .

Application

Application	Comment	Organism
drug development	mycothiol cysteine ligase (MshC) is a promising target for developing anti-mycobacterial compounds	Mycobacterium tuberculosis

Inhibitors

Inhibitors	Comment	Organism
1,3,4,6-tetra-O-acetyl-2-deoxy-2-azido-D-glucopyranose	-	Mycobacterium tuberculosis
1,3,4,6-tetra-O-acetyl-2-deoxy-2-fluoro-alpha-D-mannopyranose	-	Mycobacterium tuberculosis
1,3,4,6-tetra-O-acetyl-2-deoxy-2-fluoro-D-glucopyranose	-	Mycobacterium tuberculosis
1-D-myo-inositol 2-azido-2-deoxy-alpha-D-glucopyranoside	-	Mycobacterium tuberculosis
1-D-myo-inositol 2-fluoro-2-deoxy-alpha-D-glucopyranoside	-	Mycobacterium tuberculosis
2,3:4,5-di-O-cyclohexylidene-(1R)-menthyloxycarbonyl-D-myo-inositol	-	Mycobacterium tuberculosis
2,3:4,5-di-O-cyclohexylidene-D-myo-inositol	-	Mycobacterium tuberculosis
3,4,6-tri-O-acetyl-2-deoxy-2-azido-D-glucopyranose	-	Mycobacterium tuberculosis
3,4,6-tri-O-acetyl-2-deoxy-2-azido-D-glucopyranosyl trichloroacetimidate	-	Mycobacterium tuberculosis
3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-D-glucopyranose	-	Mycobacterium tuberculosis
3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-D-glucopyranosyl trichloroacetimidate	-	Mycobacterium tuberculosis
5'-O-(N-(L-cysteinyl)-sulfamoyl) dequalinium chloride adenosine	-	Mycobacterium tuberculosis
6-O-benzyl-2,3; 4,5-di-O-cyclohexylidene-(1R)-menthyloxycarbonyl-D-myo-inositol	-	Mycobacterium tuberculosis
6-O-benzyl-2,3; 4,5-di-O-cyclohexylidene-D-myo-inositol	-	Mycobacterium tuberculosis
6-O-benzyl-O-(3,4,6-tri-O-acetyl-2-deoxy-2-azido-alpha-D-glucopyranosyl)-(1 <->1)-2,3:4,5-di-O-cyclohexylidene-D-myo-inositol	-	Mycobacterium tuberculosis
6-O-benzyl-O-(3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-alpha-D-glucopyranosyl)-(1<->1)-2,3:4,5-di-O-cyclohexylidene-D-myo-inositol	-	Mycobacterium tuberculosis
dequalinium chloride	-	Mycobacterium tuberculosis
additional information	the enzyme structure is critical to developing potential inhibitors, synthesis of substrate analogues as potential inhibitors for the MshC enzyme. Target molecules are synthesized employing a Schmidt glycosylation strategy using an enantiomerically pure inositol acceptor and 2-deoxy trichloroacetimidate glycosyl donors with glycosylation yields greater than 70% and overall yields over 5%. The inositol acceptor is obtained via chiral resolution of myo-inositol	Mycobacterium tuberculosis
NTF1836	-	Mycobacterium tuberculosis
O-(3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-alpha-D-glucopyranosyl)-(1<->1)-2,3:4,5-di-O-cyclohexylidene-D-myo-inositol	-	Mycobacterium tuberculosis

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
1-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-1D-myo-inositol + L-cysteine + ATP	Mycobacterium tuberculosis	-	1-O-[2-(L-cysteinamido)-2-deoxy-alpha-D-glucopyranosyl]-1D-myo-inositol + AMP + diphosphate	-	?
1-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-1D-myo-inositol + L-cysteine + ATP	Mycobacterium tuberculosis ATCC 25618 / H37Rv	-	1-O-[2-(L-cysteinamido)-2-deoxy-alpha-D-glucopyranosyl]-1D-myo-inositol + AMP + diphosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Mycobacterium tuberculosis	P9WJM9	-	-
Mycobacterium tuberculosis ATCC 25618 / H37Rv	P9WJM9	-	-

Reaction

Reaction	Comment	Organism	Reaction ID
1-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-1D-myo-inositol + L-cysteine + ATP = 1-O-[2-(L-cysteinamido)-2-deoxy-alpha-D-glucopyranosyl]-1D-myo-inositol + AMP + diphosphate	the mechanism of MshC has been proposed as bi-uni-uni-bi ping pong using steady state kinetics and positional isotope exchange studies. In the first phase of the enzymatic reaction, the nucleophilic attack of carboxylate of cysteine onto the phosphate of ATP leads to the formation of the cysteine-adenylate intermediate releasing inorganic diphosphate. This cysteine-adenylate intermediate is attacked by the amine of GlcN-Ins to form Cys-GlcN-Ins and in the process releases AMP, which completes the second phase of the enzymatic reaction, overview. During this stage, the reacting substrates and coenzymes are held in place by the amino acid residues W227, H55, T46, and D251	Mycobacterium tuberculosis	a

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
1-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-1D-myo-inositol + L-cysteine + ATP	-	Mycobacterium tuberculosis	1-O-[2-(L-cysteinamido)-2-deoxy-alpha-D-glucopyranosyl]-1D-myo-inositol + AMP + diphosphate	-	?
1-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-1D-myo-inositol + L-cysteine + ATP	-	Mycobacterium tuberculosis ATCC 25618 / H37Rv	1-O-[2-(L-cysteinamido)-2-deoxy-alpha-D-glucopyranosyl]-1D-myo-inositol + AMP + diphosphate	-	?

Synonyms

Synonyms	Comment	Organism
cysS2	-	Mycobacterium tuberculosis
MshC	-	Mycobacterium tuberculosis
MTCY261.29c	-	Mycobacterium tuberculosis
mycothiol cysteine ligase	-	Mycobacterium tuberculosis
Rv2130c	-	Mycobacterium tuberculosis

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Mycobacterium tuberculosis

General Information

General Information	Comment	Organism
metabolism	mycothiol cysteine ligase (MshC) is a key enzyme in the mycothiol (MSH) biosynthesis, mycothiol biosynthesis and metabolic pathway, overview	Mycobacterium tuberculosis
physiological function	mycothiol cysteine ligase (MshC) is a key enzyme in the mycothiol (MSH) biosynthesis. The function of MshC is irreplaceable	Mycobacterium tuberculosis