8QHF

Corynebacterium glutamicum mycoloyltransferase C acyl-enzyme intermediate

Summary for 8QHF

• Entry DOI: 10.2210/pdb8qhf/pdb
• Related PRD ID: PRD_900006
• Descriptor: Cmt1, alpha-D-glucopyranose-(1-1)-alpha-D-glucopyranose, (2~{S},3~{R})-2-pentyloctane-1,3-diol, ... (6 entities in total)
• Functional Keywords: alpha / beta hydrolase, mycoloyltransferase, trehalose o- 2 mycolyltransferase, external membrane, transferase, tmm analogs
• Biological source: Corynebacterium glutamicum
• Total number of polymer chains: 1
• Total formula weight: 40333.61

Authors

Li de la Sierra-Gallay, I.,Lesur, E. (deposition date: 2023-09-08, release date: 2025-02-12, Last modification date: 2025-03-19)

Primary citation

Lesur, E.,Zhang, Y.,Dautin, N.,Dietrich, C.,Li de la Sierra-Gallay, I.,Augusto, L.A.,Rollando, P.,Lazar, N.,Urban, D.,Doisneau, G.,Constantinesco-Becker, F.,Van Tilbeurgh, H.,Guianvarc'h, D.,Bourdreux, Y.,Bayan, N.
Synthetic mycolates derivatives to decipher protein mycoloylation, a unique post-translational modification in bacteria.
J.Biol.Chem., 301:108243-108243, 2025

PubMed Abstract: Protein mycoloylation is a newly characterized post-translational modification (PTM) specifically found in Corynebacteriales, an order of bacteria that includes numerous human pathogens. Their envelope is composed of a unique outer membrane, the so-called mycomembrane made of very-long chain fatty acids, named mycolic acids. Recently, some mycomembrane proteins including PorA have been unambiguously shown to be covalently modified with mycolic acids in the model organism Corynebacterium glutamicum by a mechanism that relies on the mycoloyltransferase MytC. This PTM represents the first example of protein O-acylation in prokaryotes and the first example of protein modification by mycolic acid. Through the design and synthesis of trehalose monomycolate (TMM) analogs, we prove that i) MytC is the mycoloyltransferase directly involved in this PTM, ii) TMM, but not trehalose dimycolate (TDM), is a suitable mycolate donor for PorA mycoloylation, iii) MytC is able to discriminate between an acyl and a mycoloyl chain in vitro unlike other trehalose mycoloyltransferases. We also solved the structure of MytC acyl-enzyme obtained with a soluble short TMM analogs which constitutes the first mycoloyltransferase structure with a covalently linked to an authentic mycolic acid moiety. These data highlight the great conformational flexibility of the active site of MytC during the reaction cycle and pave the way for a better understanding of the catalytic mechanism of all members of the mycoloyltransferase family including the essential Antigen85 enzymes in Mycobacteria.

PubMed: 39880088
DOI: 10.1016/j.jbc.2025.108243

Experimental method

X-RAY DIFFRACTION (2.69 Å)