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A dynamic zinc redox switch.

Neculai AM, Neculai D, Griesinger C, Vorholt JA, Becker S
J Biol Chem 280 2826-30 (2005)
Cited: 9 times
EuropePMC logo PMID: 15548539

Abstract

The crystal structures of glutathione-dependent formaldehyde-activating enzyme (Gfa) from Paracoccus denitrificans, which catalyzes the formation of S-hydroxymethylglutathione from formaldehyde and glutathione, and its complex with glutathione (Gfa-GTT) have been determined. Gfa has a new fold with two zinc-sulfur centers, one that is structural (zinc tetracoordinated) and one catalytic (zinc apparently tricoordinated). In Gfa-GTT, the catalytic zinc is displaced due to disulfide bond formation of glutathione with one of the zinc-coordinating cysteines. Soaking crystals of Gfa-GTT with formaldehyde restores the holoenzyme. Accordingly, the displaced zinc forms a complex by scavenging formaldehyde and glutathione. The activation of formaldehyde and of glutathione in this zinc complex favors the final nucleophilic addition, followed by relocation of zinc in the catalytic site. Therefore, the structures of Gfa and Gfa-GTT draw the critical association between a dynamic zinc redox switch and a nucleophilic addition as a new facet of the redox activity of zinc-sulfur sites.

Articles - 1xa8 mentioned but not cited (2)

  1. CENP-V is required for centromere organization, chromosome alignment and cytokinesis. Tadeu AM, Ribeiro S, Johnston J, Goldberg I, Gerloff D, Earnshaw WC. EMBO J 27 2510-2522 (2008)
  2. Studies on the Glutathione-Dependent Formaldehyde-Activating Enzyme from Paracoccus denitrificans. Hopkinson RJ, Leung IK, Smart TJ, Rose NR, Henry L, Claridge TD, Schofield CJ. PLoS One 10 e0145085 (2015)


Reviews citing this publication (2)

  1. Zinc coordination environments in proteins as redox sensors and signal transducers. Maret W. Antioxid Redox Signal 8 1419-1441 (2006)
  2. Formaldehyde Stress Responses in Bacterial Pathogens. Chen NH, Djoko KY, Veyrier FJ, McEwan AG. Front Microbiol 7 257 (2016)

Articles citing this publication (5)

  1. Identification of proteins involved in formaldehyde metabolism by Rhodobacter sphaeroides. Wilson SM, Gleisten MP, Donohue TJ. Microbiology (Reading) 154 296-305 (2008)
  2. Zn2+-dependent redox switch in the intracellular T1-T1 interface of a Kv channel. Wang G, Strang C, Pfaffinger PJ, Covarrubias M. J Biol Chem 282 13637-13647 (2007)
  3. Identification of CENP-V as a novel microtubule-associating molecule that activates Src family kinases through SH3 domain interaction. Honda Z, Suzuki T, Honda H. Genes Cells 14 1383-1394 (2009)
  4. Isolation, sequencing, and heterologous expression of the Paecilomyces variotii gene encoding S-hydroxymethylglutathione dehydrogenase (fldA). Oka T, Komachi Y, Ohshima K, Kawano Y, Fukuda K, Nagahama K, Ekino K, Nomura Y. Appl Microbiol Biotechnol 99 1755-1763 (2015)
  5. Evidence of Zinc in Affording Protection Against X-Ray-Induced Brain Injury in Rats. Sharma P, Singla N, Dhawan DK. Biol Trace Elem Res 179 247-258 (2017)


Related citations provided by authors (1)

  1. A glutathione-dependent formaldehyde-activating enzyme (Gfa) from Paracoccus denitrificans detected and purified via two-dimensional proton exchange NMR spectroscopy.. Goenrich M, Bartoschek S, Hagemeier CH, Griesinger C, Vorholt JA J Biol Chem 277 3069-72 (2002)

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