Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Synonyms
ag85a, antigen 85a, ag85c, mycolyltransferase, antigen 85c, mycolyl-transferase ag85a, mycoloyl transferase,
cg0413, fbpa mycolyltransferase, alpha,alpha'-trehalose 6-monomycolate:alpha,alpha'-trehalose mycolyltransferase,
more
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
2 alpha,alpha-trehalose 6-mycolate = alpha,alpha-trehalose + alpha,alpha-trehalose 6,6'-bismycolate
2 alpha,alpha-trehalose 6-mycolate = alpha,alpha-trehalose + alpha,alpha-trehalose 6,6'-bismycolate
reaction catalyzed by antigen 85B complex involved in cell wall biosynthesis. Previously unsuspected role of 85B protein in pathogenesis of tuberculosis
-
2 alpha,alpha-trehalose 6-mycolate = alpha,alpha-trehalose + alpha,alpha-trehalose 6,6'-bismycolate
reaction catalyzed by 3 members of the Ag85 complex in vitro, namely FbpA, FbpB and FbpC2
-
2 alpha,alpha-trehalose 6-mycolate = alpha,alpha-trehalose + alpha,alpha-trehalose 6,6'-bismycolate
reaction mechanism via enzyme complexed with the tetrahedral transition state and mycolic acid covalently attached to the enzyme, the catalytic triad is formed by Ser124, Glu228 and His260
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
2 alpha,alpha-trehalose 6-mycolate
alpha,alpha-trehalose + alpha,alpha-trehalose 6,6'-bismycolate
-
-
-
-
?
alpha,alpha-trehalose 6-mycolate
alpha,alpha-trehalose + alpha,alpha-trehalose 6,6'-bismycolate
-
-
-
?
additional information
?
-
additional information
?
-
the binding of the incoming acceptor molecule drives the protein to form an active conformation, the second half-reaction could therefore proceed through a direct or indirect activation pathway upon acceptor molecule binding. The beta-hydroxy group of mycolic acid plays a direct role in the second half-reaction of Ag85 catalysis
-
-
-
additional information
?
-
-
evaluation of the substrate tolerance of Ag85 isoforms, development of a broad Ag85 substrate, overview. Modifications on every position of the sugar scaffold are tolerated, including even C-1 methyl groups at the crowded anomeric linkages, positive charges, such as in the 2-amino-trehalose and even stereochemically incorrect 2,2'-di-fluoro-alpha,beta-mannotrehalose. Even a previously reported inhibitor 6-azido-trehalose, and putative tetrahedral intermediate analogs, such as trehalose-6-phosphate, are also processed. 2,2'-dideoxy-lyxo-trehalose is no substrate
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
tetrahydrolipstatin
covalent inhibition. The enzyme undergoes structural changes upon acylation, and positioning of the peptidyl arm of tetrahydrolipstain limits hydrolysis of the acyl-enzyme adduct
(2S)-N-hydroxy-1-[4-(1,1'-biphenyl)-3,6-dihydropyridine-1(2H)-sulfonyl]piperidine-2-carboxamide
compound identified by virtual screening, shows considerable hydrogen bonds with Ag85C during 100 ns simulation and predicted to be non-hepatotoxic, non-carcinogen, non-mutagenic and non-cytotoxic
1-(3-phenoxy)benzyl 1-octanesulfonate
IC50: 0.0043 mM
1-[(2S)-2-benzyl-2-(hydroxymethyl)morpholin-4-yl]-2-pyrimidin-2-yloxyethanone
compound identified by virtual screening, shows considerable hydrogen bonds with Ag85C during 100 ns simulation and predicted to be non-hepatotoxic, non-carcinogen, non-mutagenic and non-cytotoxic
2-amino-6-propyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile
i.e. I3-AG85, enzyme inhibition leads to accumulation of trehalose monomycolate and disruption of the bacterial envelope, I3-AG85 also inhibits Mycobacterium tuberculosis survival in infected primary macrophages. Binding of I3-AG85 to Ag85C is similar to its binding to the artificial substrate octylthioglucoside, overview
2-[[[(3R*,4R*)-4-(hydroxymethyl)-1-(2-methoxy-3-methylbenzoyl)pyrrolidin-3-yl]methyl](methyl)amino]ethanol
compound identified by virtual screening, shows considerable hydrogen bonds with Ag85C during 100 ns simulation and predicted to be non-hepatotoxic, non-carcinogen, non-mutagenic and non-cytotoxic
3-Phenoxybenzyl alcohol
trehalose mimetic inhibitor
6-azido-6-deoxytrehalose
-
inhibits all three members of Ag85 complex in vitro
ethyl 3-phenoxybenzyl butylphosphonate
-
-
N-(hydroxyethyl)phthalimide
trehalose mimetic inhibitor
[(1R,2S,4S,5S,7R,9S,10S)-12-(hydroxymethyl)-4,5,15-trimethoxy-4,5-dimethyl-3,6,17-trioxatetracyclo[8.7.0.02,7.011,16]heptadeca-11,13,15-trien-9-yl]methanol
compound identified by virtual screening, shows considerable hydrogen bonds with Ag85C during 100 ns simulation and predicted to be non-hepatotoxic, non-carcinogen, non-mutagenic and non-cytotoxic
additional information
design of mechanism-based inhibitors, growth inhibition assay, molecular docking, 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl 1-butanesulfonate and 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl 1-octanesulfonate show no enzyme inhibition but are selectively cytotoxic against the breast cancer cell line MDA-MB231, overview
-
additional information
-
design and synthesis of a trehalose analogue library for identification of Ag85 inhibitors, modifications of the trehalose scaffold, overview
-
additional information
-
inhibitor screening by molecular docking, overview
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
evolution
-
members of the Ag85 family, Ag85A, Ag85B, and Ag85C, share high sequence and structural homology characterized by an alpha,beta-hydrolase fold and a hydrophobic fibronectin-binding domain. Their active sites are highly conserved, featuring a histidine, aspartic acid or glutamic acid and serine catalytic triad, a hydrophobic tunnel for the lipids and two trehalose binding sites
malfunction
inhibition of Ag85 protein family enzymes through substrate analogs hinders growth of mycobacteria and inhibition of Ag85C leads to accumulation of trehalose monomycolate
physiological function
-
the enzyme is responsible for converting trehalose monomycolate to trehalose dimycolate, which contributes to cell wall stability
physiological function
the mycoloyl transferase activity of antigen 85 (Ag85) protein family, consisting of Ag85A, -B, and -C, generates trehalose dimycolate, an envelope lipid essential for Mycobacterium tuberculosis virulence, and cell wall arabinogalactan-linked mycolic acids
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Wilkinson, R.J.; DesJardin, L.E.; Islam, N.; Gibson, B.M.; Kanost, R.A.; Wilkinson, K.A.; Poelman, D.; EisenachK.D.; Toossi, Z.
An increase in expression of a tuberculosis mycolyl transferase gene (fbpB) gene occurs early after infection of human monocytes
Mol. Microbiol.
39
813-821
2001
Mycobacterium tuberculosis
brenda
Kreme, L.; Maughan, W.N.; Wilson, R.A.; Dover, L.G.; Besra, G.S.
The M. tuberculosis antigen 85 complex and mycolyltransferase activity
Lett. Appl. Microbiol.
34
233-237
2002
Mycobacterium tuberculosis
brenda
Kovac, A.; Wilson, R.A.; Besra, G.S.; Filipic, M.; Kikelj, D.; Gobec, S.
New lipophilic phthalimido- and 3-phenoxybenzyl sulfonates: inhibition of antigen 85C mycolyltransferase activity and cytotoxicity
J. Enzyme Inhib. Med. Chem.
21
391-397
2006
Mycobacterium tuberculosis (P9WQN9), Mycobacterium tuberculosis H37Rv (P9WQN9)
brenda
Warrier, T.; Tropis, M.; Werngren, J.; Diehl, A.; Gengenbacher, M.; Schlegel, B.; Schade, M.; Oschkinat, H.; Daffe, M.; Hoffner, S.; Eddine, A.N.; Kaufmann, S.H.
Antigen 85C inhibition restricts Mycobacterium tuberculosis growth through disruption of cord factor biosynthesis
Antimicrob. Agents Chemother.
56
1735-1743
2012
Mycobacterium tuberculosis (P9WQN9), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WQN9)
brenda
Gahoi, S.; Mandal, R.S.; Ivanisenko, N.; Shrivastava, P.; Jain, S.; Singh, A.K.; Raghunandanan, M.V.; Kanchan, S.; Taneja, B.; Mandal, C.; Ivanisenko, V.A.; Kumar, A.; Kumar, R.; Open Source Drug Discovery Consortium; Ramachandran, S.
Computational screening for new inhibitors of M. tuberculosis mycolyltransferases antigen 85 group of proteins as potential drug targets
J. Biomol. Struct. Dyn.
1
30-43
2012
Mycobacterium tuberculosis
brenda
Backus, K.M.; Boshoff, H.I.; Barry, C.S.; Boutureira, O.; Patel, M.K.; DHooge, F.; Lee, S.S.; Via, L.E.; Tahlan, K.; Barry, C.E.; Davis, B.G.
Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis
Nat. Chem. Biol.
7
228-235
2011
Mycobacterium tuberculosis
brenda
Goins, C.M.; Dajnowicz, S.; Smith, M.D.; Parks, J.M.; Ronning, D.R.
Mycolyltransferase from Mycobacterium tuberculosis in covalent complex with tetrahydrolipstatin provides insights into antigen 85 catalysis
J. Biol. Chem.
293
3651-3662
2018
Mycobacterium tuberculosis (P9WQN8), Mycobacterium tuberculosis CDC 1551 (P9WQN8)
brenda
Pant, R.; Joshi, A.; Maiti, P.; Nand, M.; Pande, V.; Chandra, S.
Identification of potential mycolyltransferase Ag85C inhibitors of Mycobacterium tuberculosis H37Rv via virtual high throughput screening and binding free energy studies
J. Mol. Graph. Model.
98
107584
2020
Mycobacterium tuberculosis (P9WQP3), Mycobacterium tuberculosis, Mycobacterium tuberculosis H37Rv (P9WQP3), Mycobacterium tuberculosis H37Rv
brenda