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Literature summary for 6.2.1.45 extracted from

  • Ungermannova, D.; Parker, S.J.; Nasveschuk, C.G.; Wang, W.; Quade, B.; Zhang, G.; Kuchta, R.D.; Phillips, A.J.; Liu, X.
    Largazole and its derivatives selectively inhibit ubiquitin activating enzyme (E1) (2012), PLoS ONE, 7, e29208.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 6.2.1.45

Cloned(Commentary)

Cloned (Comment) Organism
recombinant baculovirus-mediated expression of the GST-tagged enzyme in Hi5 insect cells using the pFastBacHTA vector Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(3E)-4-[(5R,8S)-5-methyl-6,9,13-trioxo-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-trien-11-yl]but-3-en-1-yl octanoate
-
 Homo sapiens
(3E)-4-[(5R,8S)-5-methyl-6,9,13-trioxo-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-trien-11-yl]but-3-en-1-yl octanoate
-
 Schizosaccharomyces pombe
(5R,8S)-11-ethenyl-5-methyl-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
-
 Homo sapiens
(5R,8S)-11-ethenyl-5-methyl-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
-
 Schizosaccharomyces pombe
(5R,8S)-5-methyl-11-[(1E)-6-oxotridec-1-en-1-yl]-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
-
 Homo sapiens
(5R,8S)-5-methyl-11-[(1E)-6-oxotridec-1-en-1-yl]-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
-
 Schizosaccharomyces pombe
(5R,8S)-5-methyl-8-(propan-2-yl)-11-[(1E)-4-sulfanylbut-1-en-1-yl]-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
-
 Homo sapiens
(5R,8S)-5-methyl-8-(propan-2-yl)-11-[(1E)-4-sulfanylbut-1-en-1-yl]-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione
-
 Schizosaccharomyces pombe
largazole largazole and its ester and ketone analogues selectively inhibit human UBA1 enzyme and inhibit ubiquitin conjugation to cyclin-dependent kinase inhibitor p27Kip1 and TRF1 in vitro, mechanism of E1 inhibition, overview. Largazole and its derivatives specifically inhibit the adenylation step of the E1 reaction while having no effect on thioester bond formation between ubiquitin and E1. Upon incubation with E1, largazole or largazole ester reduce the amount of ubiquitin molecules that are transferred from E1 to E2 in a dose-dependent fashion. E1 inhibition appears to be specific to human E1. Largazole analogues do not significantly inhibit SUMO E1 Homo sapiens
additional information largazole and its ester and ketone analogues selectively inhibit ubiquitin conjugation to p27Kip1 and TRF1 in vitro, but the inhibition appears to be specific to human E1. Largazole analogues do not significantly inhibit Uba1p Schizosaccharomyces pombe
S-[(3E)-5-hydroxy-7-({[(4R)-4-{[(3S)-2-methoxy-4-methylpent-1-en-3-yl]carbamoyl}-4-methyl[4,5-dihydro[2,4'-bi-1,3-thiazole]]-2'-yl]methyl}amino)-7-oxohept-3-en-1-yl] octanethioate
-
 Homo sapiens
S-[(3E)-5-hydroxy-7-({[(4R)-4-{[(3S)-2-methoxy-4-methylpent-1-en-3-yl]carbamoyl}-4-methyl[4,5-dihydro[2,4'-bi-1,3-thiazole]]-2'-yl]methyl}amino)-7-oxohept-3-en-1-yl] octanethioate
-
 Schizosaccharomyces pombe
trichostatin A
-
 Schizosaccharomyces pombe

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens
Mg2+ required Schizosaccharomyces pombe

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine Homo sapiens
-
 AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
 ?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine Schizosaccharomyces pombe
-
 AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Schizosaccharomyces pombe
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant GST-tagged enzyme from Hi5 insect cells by glutathione affinity chromatography, tag cleavage by thrombin, and gel filtration Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
-
 Homo sapiens AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
 ?
ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine
-
 Schizosaccharomyces pombe AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine
-
 ?

Synonyms

Synonyms Comment Organism
E1
-
 Homo sapiens
E1
-
 Schizosaccharomyces pombe
SUMO E1
-
 Homo sapiens
Uba1
-
 Homo sapiens
UBA1p
-
 Schizosaccharomyces pombe
ubiquitin E1
-
 Homo sapiens
Ubiquitin-activating enzyme
-
 Homo sapiens
Ubiquitin-activating enzyme
-
 Schizosaccharomyces pombe

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
 assay at Homo sapiens
30
-
 assay at Schizosaccharomyces pombe

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Homo sapiens
7.5
-
 assay at Schizosaccharomyces pombe

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Homo sapiens
ATP
-
 Schizosaccharomyces pombe