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Literature summary for 2.3.1.31 extracted from

  • Chaton, C.T.; Rodriguez, E.S.; Reed, R.W.; Li, J.; Kenner, C.W.; Korotkov, K.V.
    Structural analysis of mycobacterial homoserine transacetylases central to methionine biosynthesis reveals druggable active site (2019), Sci. Rep., 9, 20267 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.3.1.31

Application

Application Comment Organism
drug development possibilty to target the methionine biosynthesis pathway, which is not part of the host metabolism, through inhibition of the enzyme, structure-based drug design Mycobacterium tuberculosis

Cloned(Commentary)

Cloned (Comment) Organism
gene metX, sequence comparisons Mycobacterium tuberculosis
gene metX, sequence comparisons Mycobacteroides abscessus
gene metX, sequence comparisons Mycolicibacterium hassiacum

Crystallization (Commentary)

Crystallization (Comment) Organism
purified enzyme, vapor diffusion hanging drop method, mixing of 0.001 ml of 13.8 mg/ml protein solution with 0.001 ml of well solution 1.2 M NaH2PO4, 0.8 M K2HPO4, 0.2 M Li sulphate, and 0.1 M CHES, pH 9.0, 18°C, several days, X-ray diffraction structure determination and analysis at 1.69-1.73 A resolution, molecular replacement using the MhMetX structure as a search model Mycobacteroides abscessus
purified enzyme, vapor diffusion hanging drop method, mixing of 0.001 ml of 13.8 mg/ml protein solution with 0.001 ml of well solution containing 0.1 M Tris-HCl, pH 8.5, and 1.8 M magnesium sulfate, 18°C, several days, X-ray diffraction structure determination and analysis at 1.90-1.95 A resolution, molecular replacement using the MaMetX structure as a search model Mycobacterium tuberculosis
purified enzyme, vapor diffusion hanging drop method, mixing of 0.001 ml of 13.8 mg/ml protein solution with 0.001 ml of well solution containing 0.2 M Ca acetate, and 20% PEG 3350, 18°C, several days, X-ray diffraction structure determination and analysis at 1.47-1.51 A resolution, molecular replacement using the structure of homoserine O-acetyltransferase from Bacillus anthracis (PDB ID 3I1I) as a search model Mycolicibacterium hassiacum

Protein Variants

Protein Variants Comment Organism
additional information construction of truncated enzyme and isolated active site Mycobacterium tuberculosis
additional information construction of truncated enzyme and isolated active site Mycobacteroides abscessus
additional information construction of truncated enzyme and isolated active site Mycolicibacterium hassiacum

Inhibitors

Inhibitors Comment Organism Structure
additional information structure-based drug design for MetX inhibition the enzyme has a highly druggable active site Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
acetyl-CoA + L-homoserine Mycobacterium tuberculosis
-
 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine Mycobacteroides abscessus
-
 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine Mycolicibacterium hassiacum
-
 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine Mycobacteroides abscessus JCM 13569
-
 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine Mycolicibacterium hassiacum DSM 44199
-
 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine Mycolicibacterium hassiacum JCM 12690
-
 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine Mycolicibacterium hassiacum CIP 105218
-
 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine Mycobacteroides abscessus CIP 104536
-
 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine Mycobacteroides abscessus DSM 44196
-
 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine Mycobacteroides abscessus ATCC 19977
-
 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine Mycolicibacterium hassiacum 3849
-
 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine Mycobacteroides abscessus NCTC 13031
-
 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine Mycobacteroides abscessus TMC 1543
-
 CoA + O-acetyl-L-homoserine
-
 ?

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WJY9
-
-
Mycobacteroides abscessus B1MG17 i.e. Mycolicibacterium abscessus or Mycobacterium abscessus
-
Mycobacteroides abscessus ATCC 19977 B1MG17 i.e. Mycolicibacterium abscessus or Mycobacterium abscessus
-
Mycobacteroides abscessus CIP 104536 B1MG17 i.e. Mycolicibacterium abscessus or Mycobacterium abscessus
-
Mycobacteroides abscessus DSM 44196 B1MG17 i.e. Mycolicibacterium abscessus or Mycobacterium abscessus
-
Mycobacteroides abscessus JCM 13569 B1MG17 i.e. Mycolicibacterium abscessus or Mycobacterium abscessus
-
Mycobacteroides abscessus NCTC 13031 B1MG17 i.e. Mycolicibacterium abscessus or Mycobacterium abscessus
-
Mycobacteroides abscessus TMC 1543 B1MG17 i.e. Mycolicibacterium abscessus or Mycobacterium abscessus
-
Mycolicibacterium hassiacum K5B926 i.e. Mycolicibacterium hassiacum
-
Mycolicibacterium hassiacum 3849 K5B926 i.e. Mycolicibacterium hassiacum
-
Mycolicibacterium hassiacum CIP 105218 K5B926 i.e. Mycolicibacterium hassiacum
-
Mycolicibacterium hassiacum DSM 44199 K5B926 i.e. Mycolicibacterium hassiacum
-
Mycolicibacterium hassiacum JCM 12690 K5B926 i.e. Mycolicibacterium hassiacum
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
acetyl-CoA + L-homoserine
-
 Mycobacterium tuberculosis CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine
-
 Mycobacteroides abscessus CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine
-
 Mycolicibacterium hassiacum CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine
-
 Mycobacteroides abscessus JCM 13569 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine
-
 Mycolicibacterium hassiacum DSM 44199 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine
-
 Mycolicibacterium hassiacum JCM 12690 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine
-
 Mycolicibacterium hassiacum CIP 105218 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine
-
 Mycobacteroides abscessus CIP 104536 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine
-
 Mycobacteroides abscessus DSM 44196 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine
-
 Mycobacteroides abscessus ATCC 19977 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine
-
 Mycolicibacterium hassiacum 3849 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine
-
 Mycobacteroides abscessus NCTC 13031 CoA + O-acetyl-L-homoserine
-
 ?
acetyl-CoA + L-homoserine
-
 Mycobacteroides abscessus TMC 1543 CoA + O-acetyl-L-homoserine
-
 ?

Synonyms

Synonyms Comment Organism
homoserine transacetylase
-
 Mycobacterium tuberculosis
homoserine transacetylase
-
 Mycobacteroides abscessus
homoserine transacetylase
-
 Mycolicibacterium hassiacum
HTA
-
 Mycobacterium tuberculosis
HTA
-
 Mycobacteroides abscessus
HTA
-
 Mycolicibacterium hassiacum
MaHTA
-
 Mycobacteroides abscessus
MaMetX
-
 Mycobacteroides abscessus
MetX
-
 Mycobacterium tuberculosis
MetX
-
 Mycobacteroides abscessus
MetX
-
 Mycolicibacterium hassiacum
MetXA
-
 Mycobacterium tuberculosis
MetXA
-
 Mycolicibacterium hassiacum
metX_2
-
 Mycolicibacterium hassiacum
MhHTA
-
 Mycolicibacterium hassiacum
MhMetX
-
 Mycolicibacterium hassiacum
MtHTA
-
 Mycobacterium tuberculosis
MtMetX
-
 Mycobacterium tuberculosis

Cofactor

Cofactor Comment Organism Structure
acetyl-CoA
-
 Mycobacterium tuberculosis
acetyl-CoA
-
 Mycobacteroides abscessus
acetyl-CoA
-
 Mycolicibacterium hassiacum

General Information

General Information Comment Organism
evolution the organization of the catalytic domains' fold marks MetX as members of the alpha/beta-hydrolase superfamily. It is a highly diverse family that includes proteases, lipases, and esterases, among many others. A canonical 8-stranded beta-sheet fold with twisted, parallel topology forms the core of alpha/beta-hydrolases. Several alpha-helices flank either face of this fold, though their number and location are different depending on the specific protein. The catalytic domain comprises residues 15-181, 297-372 of MhMetX, residues 17-183, 304-379 of MaMetX, and residues 17-181, 311-372 of MtMetX. The catalytic domain contains the active site tunnel with its a canonical catalytic triad. The catalytic triad of nucleophile-His-acid is the alpha/beta-hydrolase family's most conserved feature. Just as in other known HTA structures, MtHTA, MhHTA, and MaHTA contain a serine, aspartic acid, and histidine in the active site. HTAs have a serine between beta7 and alpha3, an aspartic acid on the loop between beta9 and alpha6, and histidine on alpha7 for these residues. For MtHTA and MhHTA, Ser157, Asp320, and His350 comprise the active site. MaHTA's triad is comprised of Ser160, Asp327, His357. The catalytic serine sits at the end of a deep catalytic tunnel Mycobacterium tuberculosis
evolution the organization of the catalytic domains' fold marks MetX as members of the alpha/beta-hydrolase superfamily. It is a highly diverse family that includes proteases, lipases, and esterases, among many others. A canonical 8-stranded beta-sheet fold with twisted, parallel topology forms the core of alpha/beta-hydrolases. Several alpha-helices flank either face of this fold, though their number and location are different depending on the specific protein. The catalytic domain comprises residues 15-181, 297-372 of MhMetX, residues 17-183, 304-379 of MaMetX, and residues 17-181, 311-372 of MtMetX. The catalytic domain contains the active site tunnel with its a canonical catalytic triad. The catalytic triad of nucleophile-His-acid is the alpha/beta-hydrolase family's most conserved feature. Just as in other known HTA structures, MtHTA, MhHTA, and MaHTA contain a serine, aspartic acid, and histidine in the active site. HTAs have a serine between beta7 and alpha3, an aspartic acid on the loop between beta9 and alpha6, and histidine on alpha7 for these residues. For MtHTA and MhHTA, Ser157, Asp320, and His350 comprise the active site. MaHTA's triad is comprised of Ser160, Asp327, His357. The catalytic serine sits at the end of a deep catalytic tunnel Mycobacteroides abscessus
evolution the organization of the catalytic domains' fold marks MetX as members of the alpha/beta-hydrolase superfamily. It is a highly diverse family that includes proteases, lipases, and esterases, among many others. A canonical 8-stranded beta-sheet fold with twisted, parallel topology forms the core of alpha/beta-hydrolases. Several alpha-helices flank either face of this fold, though their number and location are different depending on the specific protein. The catalytic domain comprises residues 15-181, 297-372 of MhMetX, residues 17-183, 304-379 of MaMetX, and residues 17-181, 311-372 of MtMetX. The catalytic domain contains the active site tunnel with its a canonical catalytic triad. The catalytic triad of nucleophile-His-acid is the alpha/beta-hydrolase family's most conserved feature. Just as in other known HTA structures, MtHTA, MhHTA, and MaHTA contain a serine, aspartic acid, and histidine in the active site. HTAs have a serine between beta7 and alpha3, an aspartic acid on the loop between beta9 and alpha6, and histidine on alpha7 for these residues. For MtHTA and MhHTA, Ser157, Asp320, and His350 comprise the active site. MaHTA's triad is comprised of Ser160, Asp327, His357. The catalytic serine sits at the end of a deep catalytic tunnel Mycolicibacterium hassiacum
metabolism the mycobacterial homoserine transacetylases is central to methionine biosynthesis Mycobacterium tuberculosis
metabolism the mycobacterial homoserine transacetylases is central to methionine biosynthesis Mycobacteroides abscessus
metabolism the mycobacterial homoserine transacetylases is central to methionine biosynthesis Mycolicibacterium hassiacum
additional information structure determination and comparison to structures of the Mycolicibacterium abscessus (MaMetX) and Mycolicibacterium hassiacum (MhMetX) MetX enzymes, homology structure modelling with bound cofactors of MetX(15-70), analysis of the potential ligandability of MetX. Two copies of each monomer exist in the asymmetric unit of all three structures. MetX can be divided into two distinct structural domains, the catalytic domain, and the lid domain. Active site structure and catalytic mechanism, overview Mycobacterium tuberculosis
additional information structure determination and comparison to structures of the Mycolicibacterium abscessus (MaMetX) and Mycolicibacterium tuberculosis (MtMetX) MetX enzymes, homology structure modelling with bound cofactors of MetX(77-372), analysis of the potential ligandability of MetX. Two copies of each monomer exist in the asymmetric unit of all three structures. MetX can be divided into two distinct structural domains, the catalytic domain, and the lid domain. Active site structure and catalytic mechanism, overview Mycolicibacterium hassiacum
additional information structure determination and comparison to structures of the Mycolicibacterium tuberculosis (MtMetX) and Mycolicibacterium hassiacum (MhMetX) MetX enzymes, homology structure modelling with bound cofactors of MetX(10-379), analysis of the potential ligandability of MetX. Two copies of each monomer exist in the asymmetric unit of all three structures. MetX can be divided into two distinct structural domains, the catalytic domain, and the lid domain. Active site structure and catalytic mechanism, overview Mycobacteroides abscessus
physiological function the homoserine transacetylase MetX converts L-homoserine to O-acetyl-L-homoserine at the committed step of the methionine biosynthesis pathway Mycobacterium tuberculosis
physiological function the homoserine transacetylase MetX converts L-homoserine to O-acetyl-L-homoserine at the committed step of the methionine biosynthesis pathway Mycobacteroides abscessus
physiological function the homoserine transacetylase MetX converts L-homoserine to O-acetyl-L-homoserine at the committed step of the methionine biosynthesis pathway Mycolicibacterium hassiacum