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Literature summary for 4.2.1.157 extracted from
- The changes in mycolic acid structures caused by hadC mutation have a dramatic effect on the virulence of Mycobacterium tuberculosis (2016), Mol. Microbiol., 99, 794-807 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| genes hadB and hadC are encoded in the hadABC locus | Mycobacterium tuberculosis |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | deletion of hadC, phenotype, overview | Mycobacterium tuberculosis |
| additional information | mutation or deletion of hadC, phenotype, overview. The hadC allele of that Mycobacterium tuberculosis strain H37Ra contains the previously reported single nucleotide insertion (C) in a GC rich region at base pair 88 (Rv0637 numbering), that it causes a frameshift in MRA0648, generating an early stop codon. The deletion mutant is termed H37RaDELTAhadC. No complementation is observed after transformation of Mycobacterium tuberculosis H37RvDELTAhadC mutant with hadC allele from Mycobacterium tuberculosis H37Ra (hadCRa), and the complete deletion of this allele in H37Ra does not significantly affect the mycolic distribution. Complementation of Mycobacterium tuberculosis strain H37Ra with either the wild-type hadC (hadCRv) or both wild-type hadB and hadC allele(s) (hadBCRv) from Mycobacterium tuberculosis strain H37Rv results in similar intermediate phenotypes | Mycobacterium tuberculosis |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| (R)-2-hydroxy-4-methylpentanoyl-CoA | Mycobacterium tuberculosis | - |
4-methylpent-2-enoyl-CoA + H2O | - |
? |  |
| (R)-2-hydroxy-4-methylpentanoyl-CoA | Mycobacterium tuberculosis ATCC 25618/ H37Rv | - |
4-methylpent-2-enoyl-CoA + H2O | - |
? | |
| (R)-2-hydroxy-4-methylpentanoyl-CoA | Mycobacterium tuberculosis ATCC 25177 / H37Ra | - |
4-methylpent-2-enoyl-CoA + H2O | - |
? | |
| additional information | Mycobacterium tuberculosis | 1H-NMR analysis of the unsaturations in the mycolic acid of different Mycobacterium tuberculosis wild-type and mutant strains, overview | ? | - |
? | |
| additional information | Mycobacterium tuberculosis ATCC 25618/ H37Rv | 1H-NMR analysis of the unsaturations in the mycolic acid of different Mycobacterium tuberculosis wild-type and mutant strains, overview | ? | - |
? | |
| additional information | Mycobacterium tuberculosis ATCC 25177 / H37Ra | 1H-NMR analysis of the unsaturations in the mycolic acid of different Mycobacterium tuberculosis wild-type and mutant strains, overview | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Mycobacterium tuberculosis | - |
- |
- |
| Mycobacterium tuberculosis | I6WYY7 AND P9WFJ9 | genes hadB and hadC, or Rv0636 and Rv0637, respectively | - |
| Mycobacterium tuberculosis ATCC 25177 / H37Ra | - |
- |
- |
| Mycobacterium tuberculosis ATCC 25618/ H37Rv | I6WYY7 AND P9WFJ9 | genes hadB and hadC, or Rv0636 and Rv0637, respectively | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| (R)-2-hydroxy-4-methylpentanoyl-CoA | - |
Mycobacterium tuberculosis | 4-methylpent-2-enoyl-CoA + H2O | - |
? | |
| (R)-2-hydroxy-4-methylpentanoyl-CoA | - |
Mycobacterium tuberculosis ATCC 25618/ H37Rv | 4-methylpent-2-enoyl-CoA + H2O | - |
? | |
| (R)-2-hydroxy-4-methylpentanoyl-CoA | - |
Mycobacterium tuberculosis ATCC 25177 / H37Ra | 4-methylpent-2-enoyl-CoA + H2O | - |
? | |
| additional information | 1H-NMR analysis of the unsaturations in the mycolic acid of different Mycobacterium tuberculosis wild-type and mutant strains, overview | Mycobacterium tuberculosis | ? | - |
? | |
| additional information | 1H-NMR analysis of the unsaturations in the mycolic acid of different Mycobacterium tuberculosis wild-type and mutant strains, overview | Mycobacterium tuberculosis ATCC 25618/ H37Rv | ? | - |
? | |
| additional information | 1H-NMR analysis of the unsaturations in the mycolic acid of different Mycobacterium tuberculosis wild-type and mutant strains, overview | Mycobacterium tuberculosis ATCC 25177 / H37Ra | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| HadBC dehydratase | - |
Mycobacterium tuberculosis |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | Mycobacterium tuberculosis strain H37Ra describes a 1 bp insertion in the MRA0648 gene, the orthologue of the Rv0637 (hadC) gene of Mycobacterium tuberculosis strain H37Rv | Mycobacterium tuberculosis |
| malfunction | mutation or deletion of hadC affects the biosynthesis of oxygenated mycolic acids, substantially reducing their production level. Myxolic acid distribution is strongly affected by hadC mutation or deletion in Mtb H37Rv with a decrease in the methoxy-mycolic acid content compensated by an increase in alpha-mycolic acids. Additionally, it causes the loss of atypical extra-long mycolic acids. These events have an impact on the morphotype, cording capacity and biofilm growth of the bacilli as well as on their sensitivity to agents such as rifampicin. Deletion of hadC also leads to a dramatic loss of virulence: an almost 4-log drop of the bacterial load in the lungs and spleens of infected immunodeficient mice. Mycolic acids of Mycobacterium tuberculosis and impact of hadC mutation on their relative distribution, Effect of hadC mutation on the morphotype, biofilm growth, tolerance to stresses and virulence of Mycobacterium tuberculosis, phenotypes, detailed overview | Mycobacterium tuberculosis |
| malfunction | mutation or deletion of hadC does not affect the growth of Mycobacterium tuberculosis. Myxolic acid distribution is strongly affected by hadC mutation or deletion in Mtb H37Ra with a decrease in the methoxy-mycolic acid content compensated by an increase in alpha-mycolic acids. Complementation of Mycobacterium tuberculosis strain H37Ra with either the wild-type hadC (hadCRv) or both wild-type hadB and hadC allele(s) (hadBCRv) from Mycobacterium tuberculosis strain H37Rv results in similar intermediate phenotypes. Effect of hadC mutation on the morphotype, biofilm growth, tolerance to stresses and virulence of Mycobacterium tuberculosis. Phenotypes, detailed overview | Mycobacterium tuberculosis |
| physiological function | involvement of HadBC in the late elongation steps of mycolic acid biosynthesis, involvement of hadC gene in the biosynthesis of atypical extra-long mycolic acids | Mycobacterium tuberculosis |
| physiological function | involvement of HadBC in the late elongation steps of mycolic acid biosynthesis, involvement of hadC gene in the biosynthesis of atypical extra-long mycolic acids. Gene hadC is not essential for Mycobacterium tuberculosis growth, inactivity of the hadC gene of H37Ra. Mycolic acids are involved in the pathogenicity of mycobacteria suggesting that there might be a link between the mutation in hadC and the attenuation of Mtb H37Ra | Mycobacterium tuberculosis |
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