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Literature summary for 6.3.1.19 extracted from

  • Zhang, S.; Burns-Huang, K.; Janssen, G.; Li, H.; Ovaa, H.; Hedstrom, L.; Darwin, K.
    Mycobacterium tuberculosis proteasome accessory factor A (PafA) can transfer prokaryotic ubiquitin-like protein (Pup) between substrates (2017), mBio, 8, e00122-17 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 6.3.1.19

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.
ATP + [prokaryotic ubiquitin-like protein]-L-glutamate + [protein]-L-lysine Mycobacterium tuberculosis
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 ADP + phosphate + N6-([prokaryotic ubiquitin-like protein]-gamma-L-glutamyl)-[protein]-L-lysine
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 ?
ATP + [prokaryotic ubiquitin-like protein]-L-glutamate + [protein]-L-lysine Mycobacterium tuberculosis ATCC 25618 / H37Rv
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 ADP + phosphate + N6-([prokaryotic ubiquitin-like protein]-gamma-L-glutamyl)-[protein]-L-lysine
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 ?

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WNU7
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Mycobacterium tuberculosis ATCC 25618 / H37Rv P9WNU7
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-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + [prokaryotic ubiquitin-like protein]-L-glutamate + [FabD]-L-lysine FabD from Mycobacterium tuberculosis is pupylated on a preferred Lys173 Mycobacterium tuberculosis ADP + phosphate + N6-([prokaryotic ubiquitin-like protein]-gamma-L-glutamyl)-[FabD]-L-lysine
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 ?
ATP + [prokaryotic ubiquitin-like protein]-L-glutamate + [FabD]-L-lysine FabD from Mycobacterium tuberculosis is pupylated on a preferred Lys173 Mycobacterium tuberculosis ATCC 25618 / H37Rv ADP + phosphate + N6-([prokaryotic ubiquitin-like protein]-gamma-L-glutamyl)-[FabD]-L-lysine
-
 ?
ATP + [prokaryotic ubiquitin-like protein]-L-glutamate + [inositol 1-phosphate synthetase]-L-lysine
-
 Mycobacterium tuberculosis ADP + phosphate + N6-([prokaryotic ubiquitin-like protein]-gamma-L-glutamyl)-[inositol 1-phosphate synthetase]-L-lysine
-
 ?
ATP + [prokaryotic ubiquitin-like protein]-L-glutamate + [inositol 1-phosphate synthetase]-L-lysine
-
 Mycobacterium tuberculosis ATCC 25618 / H37Rv ADP + phosphate + N6-([prokaryotic ubiquitin-like protein]-gamma-L-glutamyl)-[inositol 1-phosphate synthetase]-L-lysine
-
 ?
ATP + [prokaryotic ubiquitin-like protein]-L-glutamate + [Log]-L-lysine
-
 Mycobacterium tuberculosis ADP + phosphate + N6-([prokaryotic ubiquitin-like protein]-gamma-L-glutamyl)-[Log]-L-lysine
-
 ?
ATP + [prokaryotic ubiquitin-like protein]-L-glutamate + [Log]-L-lysine
-
 Mycobacterium tuberculosis ATCC 25618 / H37Rv ADP + phosphate + N6-([prokaryotic ubiquitin-like protein]-gamma-L-glutamyl)-[Log]-L-lysine
-
 ?
ATP + [prokaryotic ubiquitin-like protein]-L-glutamate + [protein]-L-lysine
-
 Mycobacterium tuberculosis ADP + phosphate + N6-([prokaryotic ubiquitin-like protein]-gamma-L-glutamyl)-[protein]-L-lysine
-
 ?
ATP + [prokaryotic ubiquitin-like protein]-L-glutamate + [protein]-L-lysine
-
 Mycobacterium tuberculosis ATCC 25618 / H37Rv ADP + phosphate + N6-([prokaryotic ubiquitin-like protein]-gamma-L-glutamyl)-[protein]-L-lysine
-
 ?
additional information PafA can move Pup from one proteasome substrate, inositol 1-phosphate synthetase (Ino1), to two different proteins, malonyl coenzyme A (CoA)-acyl carrier protein transacylase (FabD) and lonely guy (Log). Mutagenesis of substrate FabD Lys173 to Ala results in reduced transfer of Pup from Pup-Ino1 in the transpupylation reaction. Pup-Ino1 is a better Pup donor than Pup-FabD, and transpupylation requires ATP. PafA needs depupylase activity to transfer Pup between proteins. Pupylation is a two-step reaction in which PafA uses ATP to phosphorylate a carboxylate on the C terminus of Pup, which is then attacked by the amino group of a lysine side chain Mycobacterium tuberculosis ?
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 ?
additional information PafA can move Pup from one proteasome substrate, inositol 1-phosphate synthetase (Ino1), to two different proteins, malonyl coenzyme A (CoA)-acyl carrier protein transacylase (FabD) and lonely guy (Log). Mutagenesis of substrate FabD Lys173 to Ala results in reduced transfer of Pup from Pup-Ino1 in the transpupylation reaction. Pup-Ino1 is a better Pup donor than Pup-FabD, and transpupylation requires ATP. PafA needs depupylase activity to transfer Pup between proteins. Pupylation is a two-step reaction in which PafA uses ATP to phosphorylate a carboxylate on the C terminus of Pup, which is then attacked by the amino group of a lysine side chain Mycobacterium tuberculosis ATCC 25618 / H37Rv ?
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 ?

Synonyms

Synonyms Comment Organism
PafA
-
 Mycobacterium tuberculosis
proteasome accessory factor A
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 Mycobacterium tuberculosis
Pup ligase
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 Mycobacterium tuberculosis

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Mycobacterium tuberculosis

General Information

General Information Comment Organism
evolution PafA is a member of the glutamine synthetase (GS) family of proteins Mycobacterium tuberculosis
physiological function bacteria use an intrinsically disordered protein, Pup, to mark proteins for destruction. The protein degradation machinery of Mycobacterium tuberculosis includes a proteasome and a ubiquitin-like protein (Pup). Proteasome accessory factor A (PafA) attaches Pup to proteins to target them for degradation by the proteasome. PafA can move Pup from one proteasome substrate, inositol 1-phosphate synthetase (Ino1), to two different proteins, malonyl coenzyme A (CoA)-acyl carrier protein transacylase (FabD) and lonely guy (Log). This apparent transpupylation reaction requires a previously unrecognized depupylase activity in PafA, and, surprisingly, this depupylase activity is much more efficient than the activity of the dedicated depupylase Dop (deamidase of Pup). Thus, PafA can potentially use both newly synthesized Pup and recycled Pup to doom proteins for degradation. In contrast, enzyme Dop, in addition to deamidating PupGln to PupGlu, can remove Pup from proteins, which can rescue them from proteasomal degradation. PafA, unlike Dop, can-not deamidate PupGln to PupGlu, thus, PafA amidase activity appears to be limited to pupylated proteins Mycobacterium tuberculosis