6PUX

Homoserine transacetylase MetX from Mycobacterium tuberculosis

Summary for 6PUX

• Entry DOI: 10.2210/pdb6pux/pdb
• Descriptor: Homoserine O-acetyltransferase, SULFATE ION, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: methionine biosynthesis, homoserine o-acetyltransferase, homoserine o-transacetylase, hta, metx, rv3341, transferase
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 2
• Total formula weight: 77738.61

Authors

Chaton, C.T.,Korotkov, K.V. (deposition date: 2019-07-18, release date: 2019-07-31, Last modification date: 2023-10-11)

Primary citation

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.
Sci Rep, 9:20267-20267, 2019

PubMed Abstract: 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.

PubMed: 31889085
DOI: 10.1038/s41598-019-56722-2

Experimental method

X-RAY DIFFRACTION (1.9 Å)