NMR solution structures of DsbA oxidoreductases as a component of Fragment Based Drug Design — ASN Events
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  3. NMR solution structures of DsbA oxidoreductases as a component of Fragment Based Drug Design

NMR solution structures of DsbA oxidoreductases as a component of Fragment Based Drug Design (#235)

Kieran Rimmer 1
  1. Monash University, Parkville, VIC, Australia
The enzyme DsbA is a periplasmic oxidoreductase responsible for disulfide bond formation and important in the oxidative protein folding pathway of many bacteria (1, 2). It is a key regulator of bacterial virulence in pathogenic species such as Shigella flexneri, Vibrio cholerae, Escherichia coli and Neisseria meningitidis (3, 4, 5), and therefore a drug target for treatment of these infections. As a component of our fragment-based approach to developing inhibitors of DsbA, we require structural information. Here, we present the NMR solution structures of DsbA from Klebsiella pneumoniae (KpDsbA) and Pseudomonas aeruginosa (PaDsbA). Further, we present fragment NMR binding data for each protein. The protein (NMR) backbone and side-chain assignments were assigned from 2D [15N,1H] and [13C,1H] HSQCs, 3D HNCA, 3D CBCA(CO)NH, 3D HNCACB, 3D HBHA(CBCACO)NH, 3D 15N and 13C – resolved [1H,1H] NOESY spectra, using the semi-automated assignment program 'UNIO' and the structures were solved using the torsion angle dynamics program CYANA3.0 (6, 7).
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