Disulfide Isomerization in nDsbD-DsbC Complex – Exploring an Internal Nucleophile Mediated Reaction Pathway

Nair, AG and Sravanakumar Perumalla, D and Anjukandi, P (2022) Disulfide Isomerization in nDsbD-DsbC Complex – Exploring an Internal Nucleophile Mediated Reaction Pathway. In: ChemPhysChem .

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Abstract

The disulfide bond redox chemistry of proteins is believed to be mostly governed by the proton motive force. The nucleophilic and α-elimination mechanisms are also found to supplement the formation and scission of the S−S bonds. On these grounds, the possibility for an internal nucleophile assisted disulfide bond formation in the nDsbD-DsbC complex was proposed way back. Using QM/MM MD metadynamics simulations, we explore the feasibility of the proposed mechanism. Our simulations highlight the formation of the internal nucleophile Tyr42O− and Tyr40O− which further generates Cys103S− necessary for the disulfide bond formation in nDsbD. Our results illustrate how the isomerase DsbC is functionally activated by nDsbD in gram-negative bacteria. Also, we foresee that the results will be important for modelling anti-bacterial compounds based on nDsbD.

Item Type:	Journal Article
Publication:	ChemPhysChem
Publisher:	John Wiley and Sons Inc
Additional Information:	The copyright for this article belongs to the John Wiley and Sons Inc.
Keywords:	Bacteria; Covalent bonds; Isomerization; Isomers; Molecular dynamics; Reaction kinetics; Sulfur compounds, Ab initio molecular dynamics; Disulfide bond formation; Disulfide isomerization; Disulphide bonds; Mediated reactions; Metadynamics; Proton-motive forces; Reaction pathways; Redox chemistry; α-Elimination, Nucleophiles
Department/Centre:	Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	23 Aug 2022 05:45
Last Modified:	23 Aug 2022 05:45
URI:	https://eprints.iisc.ac.in/id/eprint/76178

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