2ndo | pdb_00002ndo
Structure of EcDsbA-sulfonamide1 complex
Structural highlights
Function[DSBA_ECOLI] Required for disulfide bond formation in some periplasmic proteins such as PhoA or OmpA. Acts by transferring its disulfide bond to other proteins and is reduced in the process. DsbA is reoxidized by DsbB. Required for pilus biogenesis. PhoP-regulated transcription is redox-sensitive, being activated when the periplasm becomes more reducing (deletion of dsbA/dsbB, treatment with dithiothreitol). MgrB acts between DsbA/DsbB and PhoP/PhoQ in this pathway.[1] [2] Publication Abstract from PubMedWe describe a general approach to determine the binding pose of small molecules in weakly bound protein-ligand complexes by deriving distance constraints between the ligand and methyl groups from all methyl-containing residues of the protein. We demonstrate that using a single sample, which can be prepared without the use of expensive precursors, it is possible to generate high-resolution data rapidly and obtain the resonance assignments of Ile, Leu, Val, Ala and Thr methyl groups using triple resonance scalar correlation data. The same sample may be used to obtain Met epsilonCH3 assignments using NOESY-based methods, although the superior sensitivity of NOESY using [U-13C,15N]-labeled protein makes the use of this second sample more efficient. We describe a structural model for a weakly binding ligand bound to its target protein, DsbA, derived from intermolecular methyl-to-ligand nuclear Overhauser enhancements, and demonstrate that the ability to assign all methyl resonances in the spectrum is essential to derive an accurate model of the structure. Once the methyl assignments have been obtained, this approach provides a rapid means to generate structural models for weakly bound protein-ligand complexes. Such weak complexes are often found at the beginning of programs of fragment based drug design and can be challenging to characterize using X-ray crystallography. Determination of ligand binding modes in weak protein-ligand complexes using sparse NMR data.,Mohanty B, Williams ML, Doak BC, Vazirani M, Ilyichova O, Wang G, Bermel W, Simpson JS, Chalmers DK, King GF, Mobli M, Scanlon MJ J Biomol NMR. 2016 Nov;66(3):195-208. Epub 2016 Oct 24. PMID:27778134[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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