4B6G: The Crystal Structure of the Neisserial Esterase D

Citation:
Abstract
AIM: The glutathione-dependent AdhC-EstD formaldehyde detoxification system is found in eukaryotes and prokaryotes. It is established that it confers protection against formaldehyde that is produced from environmental sources or methanol metabolism. Thus, its presence in the human host-adapted bacterial pathogen Neisseria meningitidis is intriguing. This work defined the biological function of this system in the meningococcus using phenotypic analyses of mutants linked to biochemical and structural characterization of purified enzymes. RESULTS: We demonstrated that mutants in the adhC and/or estD were sensitive to killing by formaldehyde. Inactivation of adhC and/or estD also led to a loss of viability in biofilm communities, even in the absence of exogenous formaldehyde. Detailed biochemical and structural analyses of the esterase component demonstrated that S-formylglutathione was the only biologically relevant substrate for EstD. We further showed that an absolutely conserved cysteine residue was covalently modified by S-glutathionylation. This leads to inactivation of EstD. INNOVATION: The results provide several conceptual innovations. They provide a new insight into formaldehyde detoxification in bacteria that do not generate formaldehyde during the catabolism of methanol. Our results also indicate that the conserved cysteine, found in all EstD enzymes from humans to microbes, is a site of enzyme regulation, probably via S-glutathionylation. CONCLUSION: The adhc-estD system protects against formaldehyde produced during endogenous metabolism.
PDB ID: 4B6GDownload
MMDB ID: 104995
PDB Deposition Date: 2012/8/13
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 1.4  Å
Source Organism:
Similar Structures:
Biological Unit for 4B6G: monomeric; determined by software (PISA)
Molecular Components in 4B6G
Label Count Molecule
Protein (1 molecule)
1
Putative Esterase
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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