Gram-positive DsbE Proteins Function Differently from Gram-negative DsbE Homologs

By C. Goulding, M. Apostol, S. Gleiter, A. Parseghian, J. Bardwell, M. Gennaro, David S. Eisenberg. 2004

85 citations recorded by the source corpus.

Mycobacterium tuberculosis, a Gram-positive bacterium, encodes a secreted Dsb-like protein annotated as Mtb DsbE (Rv2878c, also known as MPT53). Because Dsb proteins in Escherichia coli and other bacteria seem to catalyze proper folding during protein secretion and because folding of secreted proteins is thought to be coupled to disulfide oxidoreduction, the function of Mtb DsbE may be to ensure that secreted proteins are in their correctly folded states. We have determined the crystal structure of Mtb DsbE to 1.1 Å resolution, which reveals a thioredoxin-like domain with a typical CXXC active site. These cysteines are in their reduced state. Biochemical characterization of Mtb DsbE reveals that this disulfide oxidoreductase is an oxidant, unlike Gram-negative bacteria DsbE proteins, which have been shown to be weak reductants. In addition, the pKa value of the active site, solvent-exposed cysteine is ∼2 pH units lower than that of Gram-negative DsbE homologs. Finally, the reduced form of Mtb DsbE is more stable than the oxidized form, and Mtb DsbE is able to oxidatively fold hirudin. Structural and biochemical analysis implies that Mtb DsbE functions differently from Gram-negative DsbE homologs, and we discuss its possible functional role in the bacterium.

Subfields: Genetics, Materials Chemistry, Molecular Biology

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In Genetics

1. Lucy J. Colwell
2. W. Pitsawong
3. Hannah K. Wayment-Steele
4. Sergey Ovchinnikov
5. Renee Otten
6. Marc Hoemberger
7. Julia M Apitz
8. Dorothee Kern

In Materials Chemistry

1. W. Pitsawong
2. Hannah K. Wayment-Steele
3. Sergey Ovchinnikov
4. Renee Otten
5. Marc Hoemberger
6. Julia M Apitz
7. Lucy J. Colwell
8. Dorothee Kern

In Molecular Biology

1. Lucy J. Colwell
2. Sergey Ovchinnikov
3. Dorothee Kern
4. Hannah K. Wayment-Steele
5. W. Pitsawong
6. Renee Otten
7. Marc Hoemberger
8. Julia M Apitz

Citations in the corpus

• Predicting multiple conformations via sequence clustering and AlphaFold2 (2023, positive): “Mpt53 is an extracellular single-domain enzyme that is suggested to ensure correct folding of several cell-wall and extracellular protein substrates in M. tuberculosis by catalysing disulfide oxidation 42 .”