The application of FAST-NMR for the identification of novel drug discovery targets

HP0902 from Helicobacter pylori is a thermostable, dimeric protein belonging to an all-β topology of the cupin superfamily

“…By proposing molecular and cellular functions for unannotated proteins, structural genomics studies of human pathogens have been useful in identifying potential drug targets and in providing critical information for structure-based drug discovery (6)(7)(8)(9)(10). In particular, NMR spectroscopy has been employed efficiently for both structural genomics (11)(12)(13) and structure-based drug discovery efforts (14)(15)(16)(17), by monitoring protein structures in a solution state. In this work, as a component of our structural genomics examinations of the human gastric pathogen Helicobacter pylori, the hypothetical protein HP0902 (UniProtKB/TrEMBL ID O25562) was investigated via NMR.…”

Spin-Lattice Relaxation Time in Drug Discovery and Design

“…The structure of the pTyr-SAV-1430 complex, obtained by NMR and Autodock [29], was used for CPASS analysis, leading to identification of a Src SH2 domain bound to pTry-containing peptide as a binding site analog with 37% similarity [18]. Those results lead to the identification of SAV1430 as an element for formation of protein-protein complexes which are essential for the bacterial viability [17].…”

“…This methodology is commonly used to identify protein and DNA ligands. Recently, this analysis was applied for the function elucidation of new unannotated proteins using FAST-NMR approach [17,18]. The FAST-NMR method is used to identify the function of new unannotated proteins by identification of their active site and its similarity with known proteins.…”

Statistical removal of background signals from high-throughput 1H NMR line-broadening ligand-affinity screens

“…NMR ligand-affinity screening is also a powerful platform for protein functional annotation during the search for novel drug targets (Mercier et al 2009; Powers et al 2008). A significant percentage of the human proteome and the proteomes of other infectious organisms is comprised of functionally uncharacterized proteins (Muller et al 2002).…”

“…As part of an NMR high-throughput screen, these 1D 1 H NMR pulse sequences present a number of unique challenges that include high false positive rates, low throughput, and high demand for protein samples (Harner et al 2013; Lepre 2011). However, at suitably chosen concentrations of ligand and protein, a standard, unedited 1D 1 H NMR experiment may be used to detect binding interactions through enhanced relaxation rates of ligand spins (Mercier et al 2006; Mercier et al 2009; Powers et al 2008). …”