Cristin-resultat-ID: 1863727
Sist endret: 8. februar 2021, 15:33
NVI-rapporteringsår: 2020
Resultat
Vitenskapelig artikkel
2020

The Crystal Structures of Bacillithiol Disulfide Reductase Bdr (YpdA) Provide Structural and Functional Insight into a New Type of FAD-Containing NADPH-Dependent Oxidoreductase

Bidragsytere:
  • Marta Hammerstad
  • Ingvild Gudim og
  • Hans-Petter Hersleth

Tidsskrift

Biochemistry
ISSN 0006-2960
e-ISSN 1520-4995
NVI-nivå 1

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2020
Volum: 59
Hefte: 51
Sider: 4793 - 4798
Open Access

Importkilder

Scopus-ID: 2-s2.0-85098753583

Klassifisering

Vitenskapsdisipliner

Kjemi

Emneord

Strukturbiologi • Biokjemi • Enzymologi

Beskrivelse Beskrivelse

Tittel

The Crystal Structures of Bacillithiol Disulfide Reductase Bdr (YpdA) Provide Structural and Functional Insight into a New Type of FAD-Containing NADPH-Dependent Oxidoreductase

Sammendrag

Low G+C Gram-positive Firmicutes, such as the clinically important pathogens Staphylococcus aureus and Bacillus cereus, use the low-molecular weight thiol bacillithiol (BSH) as a defense mechanism to buffer the intracellular redox environment and counteract oxidative stress encountered by human neutrophils during infections. The protein YpdA has recently been shown to function as an essential NADPH-dependent reductase of oxidized bacillithiol disulfide (BSSB) resulting from stress responses and is crucial for maintaining the reduced pool of BSH and cellular redox balance. In this work, we present the first crystallographic structures of YpdAs, namely, those from S. aureus and B. cereus. Our analyses reveal a uniquely organized biological tetramer; however, the structure of the monomeric subunit is highly similar to those of other flavoprotein disulfide reductases. The absence of a redox active cysteine in the vicinity of the FAD isoalloxazine ring implies a new direct disulfide reduction mechanism, which is backed by the presence of a potentially gated channel, serving as a putative binding site for BSSB in the proximity of the FAD cofactor. We also report enzymatic activities for both YpdAs, which along with the structures presented in this work provide important structural and functional insight into a new class of FAD-containing NADPH-dependent oxidoreductases, related to the emerging fight against pathogenic bacteria.

Bidragsytere

Marta Hammerstad

  • Tilknyttet:
    Forfatter
    ved Seksjon for biokjemi og molekylærbiologi ved Universitetet i Oslo

Ingvild Gudim

  • Tilknyttet:
    Forfatter
    ved Seksjon for biokjemi og molekylærbiologi ved Universitetet i Oslo

Hans-Petter Hersleth

  • Tilknyttet:
    Forfatter
    ved Seksjon for biokjemi og molekylærbiologi ved Universitetet i Oslo
  • Tilknyttet:
    Forfatter
    ved Kjemisk institutt ved Universitetet i Oslo
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