4ZIJ

Crystal structure of E.Coli DsbA in complex with 2-(4-iodophenylsulfonamido) benzoic acid

Summary for 4ZIJ

• Entry DOI: 10.2210/pdb4zij/pdb
• Descriptor: Thiol:disulfide interchange protein DsbA, 2-{[(4-iodophenyl)sulfonyl]amino}benzoic acid, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: disulfide oxidoreductase, redox protein, dsba, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 42516.95

Authors

Vazirani, M.,Ilyichova, O.V.,Scanlon, M.J. (deposition date: 2015-04-28, release date: 2016-05-11, Last modification date: 2024-11-13)

Primary citation

Mohanty, B.,Williams, M.L.,Doak, B.C.,Vazirani, M.,Ilyichova, O.,Wang, G.,Bermel, W.,Simpson, J.S.,Chalmers, D.K.,King, G.F.,Mobli, M.,Scanlon, M.J.
Determination of ligand binding modes in weak protein-ligand complexes using sparse NMR data.
J.Biomol.Nmr, 66:195-208, 2016

PubMed Abstract: We 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 CH assignments using NOESY-based methods, although the superior sensitivity of NOESY using [U-C,N]-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.

PubMed: 27778134
DOI: 10.1007/s10858-016-0067-4

Experimental method

X-RAY DIFFRACTION (1.78 Å)