One of These is Not Like the Others

Pavelka, Martin S.

doi:10.1016/j.tim.2015.09.005

Cited by 2 publications

(1 citation statement)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, it has recently been demonstrated that metX is required for maintaining bacterial survival during chronic Mtb infection 11 . Together, these data suggest that Mtb is unable to scavenge biosynthetic intermediates from the host for methionine synthesis, making for a uniquely exploitable vulnerability for the development of antibacterial agents 12 .…”

Section: Introductionmentioning

confidence: 99%

Structural analysis of mycobacterial homoserine transacetylases central to methionine biosynthesis reveals druggable active site

Chaton

Rodriguez

Reed

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Mycobacterium tuberculosis is the cause of the world’s most deadly infectious disease. Efforts are underway to target the methionine biosynthesis pathway, as it is not part of the host metabolism. The homoserine transacetylase MetX converts l-homoserine to O-acetyl-l-homoserine at the committed step of this pathway. In order to facilitate structure-based drug design, we determined the high-resolution crystal structures of three MetX proteins, including M. tuberculosis (MtMetX), Mycolicibacterium abscessus (MaMetX), and Mycolicibacterium hassiacum (MhMetX). A comparison of homoserine transacetylases from other bacterial and fungal species reveals a high degree of structural conservation amongst the enzymes. Utilizing homologous structures with bound cofactors, we analyzed the potential ligandability of MetX. The deep active-site tunnel surrounding the catalytic serine yielded many consensus clusters during mapping, suggesting that MtMetX is highly druggable.

show abstract

Section: Introductionmentioning

confidence: 99%

Structural analysis of mycobacterial homoserine transacetylases central to methionine biosynthesis reveals druggable active site

Chaton

Rodriguez

Reed

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

Structural analysis of mycobacterial homoserine transacetylases central to methionine biosynthesis reveals druggable active site

Chaton

Rodriguez

Reed

et al. 2019

Preprint

View full text Add to dashboard Cite

Mycobacterium tuberculosis is cause of the world's most deadly infectious disease. Efforts are underway to target the methionine biosynthesis pathway, as it is not part of the host metabolism. The homoserine transacetylase MetA converts L-homoserine to O-acetyl-Lhomoserine at the committed step of this pathway. In order to facilitate structure-based drug design, we determined the high-resolution crystal structures of three MetA proteins, including M. tuberculosis (MtMetA), Mycolicibacterium abscessus (MaMetA), and Mycolicibacterium hassiacum (MhMetA). Comparison to other homoserine transacetylase family-members reveals a high degree of structural conservation. Utilizing homologous structures with bound cofactors, we analyzed the potential ligandability of MetA. The deep active-site tunnel surrounding the catalytic serine yielded a number of consensus clusters during mapping, suggesting thatMtMetA is highly druggable.

show abstract

One of These is Not Like the Others

Cited by 2 publications

References 10 publications

Structural analysis of mycobacterial homoserine transacetylases central to methionine biosynthesis reveals druggable active site

Structural analysis of mycobacterial homoserine transacetylases central to methionine biosynthesis reveals druggable active site

Structural analysis of mycobacterial homoserine transacetylases central to methionine biosynthesis reveals druggable active site

Contact Info

Product

Resources

About