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 (Comment) | Organism |
---|---|
gene metX, sequence comparisons | Mycobacterium tuberculosis |
gene metX, sequence comparisons | Mycobacteroides abscessus |
gene metX, sequence comparisons | Mycolicibacterium hassiacum |
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 | 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 | Comment | Organism | Structure |
---|---|---|---|
additional information | structure-based drug design for MetX inhibition the enzyme has a highly druggable active site | Mycobacterium tuberculosis |
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 | 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 | 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 | 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 | Comment | Organism | Structure |
---|---|---|---|
acetyl-CoA | - |
Mycobacterium tuberculosis | |
acetyl-CoA | - |
Mycobacteroides abscessus | |
acetyl-CoA | - |
Mycolicibacterium hassiacum |
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 |