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MetaCyc Enzyme: antigen 85A

Gene: fbpA Accession Number: RV3804C (MetaCyc)

Synonyms: Rv3804c, mycolyl transferase 85A, fibronectin-binding protein A, secreted antigen 85-A fbpA

Species: Mycobacterium tuberculosis H37Rv

Summary:
Mycobacterium tuberculosis H37Rv expresses three closely related mycolyl tranferases, also known as the antigen 85 (Ag85) complex. All three contribute to cell wall synthesis by catalyzing transfer of mycolic acid from one trehalose 6-monomycolate (TMM) to another, forming trehalose 6,6'-dimycolate [Belisle97] as well as the transfer of mycolate from TMM to arabinogalactan, forming the cell wall arabinogalactan-mycolate polymer [Takayama05].

The three antigen 85 variants are expressed at a steady-state ratio of 3:2:1 (ag85B: ag85A:ag85C), making antigen 85B the most abundant protein exported by M. tuberculosis (although it is the least active of the three) [Anderson01].

antigen 85A is the basis of a new tuberculosis vaccine, MVA85A [Sander09, Whelan09]. It is also regarded as an important potential drug target [Elamin09].

Gene Citations: [Lee95, Wiker90]

Map Position: [4,265,639 <- 4,266,655] (96.69 centisomes)

Molecular Weight of Polypeptide: 35.686 kD (from nucleotide sequence)

Unification Links: Entrez-gene:886132 , Pride:P0A4V2 , Protein Model Portal:P0A4V2 , SMR:P0A4V2 , String:83332.Rv3804c , UniProt:P0A4V2

Relationship Links: InterPro:IN-FAMILY:IPR000801 , InterPro:IN-FAMILY:IPR006311 , PDB:Structure:1SFR , Pfam:IN-FAMILY:PF00756 , Prosite:IN-FAMILY:PS51318

Gene-Reaction Schematic: ?

Credits:
Revised 17-Dec-2009 by Caspi R , SRI International


Enzymatic reaction of: arabinogalactan:trehalose-trans-keto-mycolate mycolyltransferase (antigen 85A)

EC Number: 2.3.1.-

a mycobacterial arabinogalactan + trehalose-trans-keto-mono-mycolate <=> arabinogalactan-trans-keto-mycolate + α,α-trehalose

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of mycolate biosynthesis , mycolate biosynthesis

Summary:
antigen 85A is an extracellular mycolyltransferase that catalyzes the transfer of mycolic acid from a trehalose-trans-keto-mono-mycolate to an arabinogalactan to form cell-wall arabinogalactan-trans-keto-mycolate outside the cells. antigen 85A shares 65 to 80 percent identity with antigen 85B and antigen 85C [Takayama05]. Overproduction of antigen 85A in the fbpC-inactivated mutant strain of M. tuberculosis restored the cell wall-linked mycolate defect [Puech02].

Citations: [Belisle97]


Enzymatic reaction of: arabinogalactan:trehalose-cis-keto-mycolate mycolyltransferase (antigen 85A)

EC Number: 2.3.1.-

a mycobacterial arabinogalactan + trehalose-cis-keto-mono-mycolate <=> arabinogalactan-cis-keto-mycolate + α,α-trehalose

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of mycolate biosynthesis , mycolate biosynthesis

Summary:
antigen 85A is an extracellular mycolyltransferase that catalyzes the transfer of mycolic acid from a trehalose-cis-keto-mono-mycolate to an arabinogalactan to form cell-wall arabinogalactan-cis-keto-mycolate outside the cells. antigen 85A shares 65 to 80 percent identity with antigen 85B and antigen 85C [Takayama05]. Overproduction of antigen 85A in the fbpC-inactivated mutant strain of M. tuberculosis restored the cell wall-linked mycolate defect [Puech02].

Citations: [Belisle97]


Enzymatic reaction of: arabinogalactan:trehalose-trans-methoxy-mono-mycolate mycolyltransferase (antigen 85A)

EC Number: 2.3.1.-

a mycobacterial arabinogalactan + trehalose-trans-methoxy-mono-mycolate <=> arabinogalactan-trans-methoxy-mycolate + α,α-trehalose

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of mycolate biosynthesis , mycolate biosynthesis

Summary:
antigen 85A is an extracellular mycolyltransferase that catalyzes the transfer of mycolic acid from a trehalose-trans-methoxy-mono-mycolate to an arabinogalactan to form cell-wall arabinogalactan-trans-methoxy-mycolate outside the cells. antigen 85A shares 65 to 80 percent identity with antigen 85B and antigen 85C [Takayama05]. Overproduction of antigen 85A in the fbpC-inactivated mutant strain of M. tuberculosis restored the cell wall-linked mycolate defect [Puech02].


Enzymatic reaction of: arabinogalactan: trehalose-cis-methoxy-mycolate mycolyltransferase (antigen 85A)

EC Number: 2.3.1.-

a mycobacterial arabinogalactan + trehalose-cis-methoxy-mono-mycolate <=> arabinogalactan-cis-methoxy-mycolate + α,α-trehalose

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of mycolate biosynthesis , mycolate biosynthesis

Summary:
antigen 85A is an extracellular mycolyltransferase that catalyzes the transfer of mycolic acid from a trehalose-cis-methoxy-mono-mycolate to an arabinogalactan to form cell-wall arabinogalactan-cis-methoxy-mycolate outside the cells. antigen 85A shares 65 to 80 percent identity with antigen 85B and antigen 85C [Takayama05]. Overproduction of antigen 85A in the fbpC-inactivated mutant strain of M. tuberculosis restored the cell wall-linked mycolate defect [Puech02].


Enzymatic reaction of: arabinogalactan: trehalose-mono-mycolate mycolyltransferase (antigen 85A)

EC Number: 2.3.1.-

a mycobacterial arabinogalactan + trehalose-mono-mycolate <=> mycolyl-arabinogalactan-peptidoglycan complex + α,α-trehalose

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of mycolyl-arabinogalactan-peptidoglycan complex biosynthesis , superpathway of mycolate biosynthesis , mycolyl-arabinogalactan-peptidoglycan complex biosynthesis , mycolate biosynthesis

Summary:
antigen 85A is an extracellular mycolyltransferase that catalyzes the transfer of mycolic acid from a trehalose-mono-mycolate to an arabinogalactan to form cell-wall mycolyl-arabinogalactan-peptidoglycan complex outside the cells. antigen 85A shares 65 to 80 percent identity with antigen 85B and antigen 85C [Takayama05]. Overproduction of antigen 85A in the fbpC-inactivated mutant strain of M. tuberculosis restored the cell wall-linked mycolate defect [Puech02].


Enzymatic reaction of: trehalose-trans-keto-mycolate:trehalose-trans-keto-mycolate 6-mycolyltransferase (antigen 85A)

EC Number: 2.3.1.-

2 trehalose-trans-keto-mono-mycolate[periplasmic space] <=> trehalose-trans-keto-di-mycolate[periplasmic space] + α,α-trehalose[periplasmic space]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of mycolate biosynthesis , mycolate biosynthesis

Summary:
antigen 85A is an extracellular mycolyltransferase that catalyzes the transfer of mycolic acid from a trehalose-trans-keto-mono-mycolate to another trehalose-trans-keto-mono-mycolate form trehalose-trans-keto-di-mycolate outside the cells. antigen 85A shares 65 to 80 percent identity with antigen 85B and antigen 85C [Takayama05]. TLC shows that TDM is formed by antigen 85A in mycolyltransferase assay [Belisle97].


Enzymatic reaction of: trehalose-cis-keto-mycolate:trehalose-cis-keto-mycolate 6-mycolyltransferase (antigen 85A)

EC Number: 2.3.1.-

2 trehalose-cis-keto-mono-mycolate[periplasmic space] <=> trehalose-cis-keto-di-mycolate[periplasmic space] + α,α-trehalose[periplasmic space]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of mycolate biosynthesis , mycolate biosynthesis

Summary:
antigen 85A is an extracellular mycolyltransferase that catalyzes the transfer of mycolic acid from a trehalose-cis-keto-mono-mycolate to another trehalose-cis-keto-mono-mycolate form trehalose-cis-keto-di-mycolate outside the cells. antigen 85A shares 65 to 80 percent identity with antigen 85B and antigen 85C [Takayama05]. TLC shows that TDM is formed by antigen 85A in mycolyltransferase assay [Belisle97].


Enzymatic reaction of: trehalose-trans-methoxy-mono-mycolate:trehalose-trans-methoxy-mono-mycolate 6-mycolyltransferase (antigen 85A)

EC Number: 2.3.1.-

2 trehalose-trans-methoxy-mono-mycolate[periplasmic space] <=> trehalose-trans-methoxy-di-mycolate[periplasmic space] + α,α-trehalose[periplasmic space]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of mycolate biosynthesis , mycolate biosynthesis

Summary:
antigen 85A is an extracellular mycolyltransferase that catalyzes the transfer of mycolic acid from a trehalose-trans-methoxy-mono-mycolate to another trehalose-trans-methoxy-mono-mycolate form trehalose-trans-methoxy-di-mycolate outside the cells. antigen 85A shares 65 to 80 percent identity with antigen 85B and antigen 85C [Takayama05]. TLC shows that TDM is formed by antigen 85A in mycolyltransferase assay [Belisle97].


Enzymatic reaction of: trehalose-cis-methoxy-mycolate:trehalose-cis-methoxy-mycolate 6-mycolyltransferase (antigen 85A)

EC Number: 2.3.1.-

2 trehalose-cis-methoxy-mono-mycolate[periplasmic space] <=> trehalose-cis-methoxy-di-mycolate[periplasmic space] + α,α-trehalose[periplasmic space]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is favored in the direction shown.

In Pathways: superpathway of mycolate biosynthesis , mycolate biosynthesis

Summary:
antigen 85A is an extracellular mycolyltransferase that catalyzes the transfer of mycolic acid from a trehalose-cis-methoxy-mono-mycolate to another trehalose-cis-methoxy-mono-mycolate form trehalose-cis-methoxy-di-mycolate outside the cells. antigen 85A shares 65 to 80 percent identity with antigen 85B and antigen 85C [Takayama05]. TLC shows that TDM is formed by antigen 85A in mycolyltransferase assay [Belisle97].


Enzymatic reaction of: α,α-trehalose-6-mycolate:α,α-trehalose-6-mycolate 6-mycolyltransferase (antigen 85A)

EC Number: 2.3.1.122

2 trehalose-mono-mycolate <=> α, α'-trehalose 6,6'-bismycolate + α,α-trehalose

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: superpathway of mycolate biosynthesis , mycolate biosynthesis

Summary:
antigen 85A is an extracellular mycolyltransferase that catalyzes the transfer of mycolic acid from a trehalose-mono-mycolate to another trehalose-mono-mycolate form trehalose-di-mycolate outside the cells. antigen 85A shares 65 to 80 percent identity with antigen 85B and antigen 85C [Takayama05]. TLC shows that TDM is formed by antigen 85A in mycolyltransferase assay [Belisle97].


References

Anderson01: Anderson DH, Harth G, Horwitz MA, Eisenberg D (2001). "An interfacial mechanism and a class of inhibitors inferred from two crystal structures of the Mycobacterium tuberculosis 30 kDa major secretory protein (Antigen 85B), a mycolyl transferase." J Mol Biol 307(2);671-81. PMID: 11254389

Belisle97: Belisle JT, Vissa VD, Sievert T, Takayama K, Brennan PJ, Besra GS (1997). "Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis." Science 276(5317);1420-2. PMID: 9162010

Elamin09: Elamin AA, Stehr M, Oehlmann W, Singh M (2009). "The mycolyltransferase 85A, a putative drug target of Mycobacterium tuberculosis: development of a novel assay and quantification of glycolipid-status of the mycobacterial cell wall." J Microbiol Methods 79(3);358-63. PMID: 19857528

Lee95: Lee BY, Horwitz MA (1995). "Identification of macrophage and stress-induced proteins of Mycobacterium tuberculosis." J Clin Invest 96(1);245-9. PMID: 7615794

Puech02: Puech V, Guilhot C, Perez E, Tropis M, Armitige LY, Gicquel B, Daffe M (2002). "Evidence for a partial redundancy of the fibronectin-binding proteins for the transfer of mycoloyl residues onto the cell wall arabinogalactan termini of Mycobacterium tuberculosis." Mol Microbiol 44(4);1109-22. PMID: 12010501

Sander09: Sander CR, Pathan AA, Beveridge NE, Poulton I, Minassian A, Alder N, Van Wijgerden J, Hill AV, Gleeson FV, Davies RJ, Pasvol G, McShane H (2009). "Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in Mycobacterium tuberculosis-infected individuals." Am J Respir Crit Care Med 179(8);724-33. PMID: 19151191

Takayama05: Takayama K, Wang C, Besra GS (2005). "Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis." Clin Microbiol Rev 18(1);81-101. PMID: 15653820

Whelan09: Whelan KT, Pathan AA, Sander CR, Fletcher HA, Poulton I, Alder NC, Hill AV, McShane H (2009). "Safety and immunogenicity of boosting BCG vaccinated subjects with BCG: comparison with boosting with a new TB vaccine, MVA85A." PLoS One 4(6);e5934. PMID: 19529780

Wiker90: Wiker HG, Sletten K, Nagai S, Harboe M (1990). "Evidence for three separate genes encoding the proteins of the mycobacterial antigen 85 complex." Infect Immun 58(1);272-4. PMID: 2403534


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sun Dec 21, 2014, biocyc13.