title: Characterization of the Binding of Hydroxyindole, Indoleacetic acid, and Morpholinoaniline to the Salmonella Type III Secretion System Proteins SipD and SipB.
abstract: Many Gram-negative bacteria require the type III secretion system (T3SS) to cause infectious diseases in humans. A looming public health problem is that all bacterial pathogens that require the T3SS to cause infectious diseases in humans have developed multidrug resistance to current antibiotics. The T3SS is an attractive target for the development of new antibiotics because of its critical role in virulence. An initial step in developing anti-T3SS-based therapeutics is the identification of small molecules that can bind to T3SS proteins. Currently, the only small molecules that are known to bind to the Salmonella T3SS proteins SipD and SipB are bile salts (to SipD) and sphingolipids and cholesterol (to SipB). Herein we report the results of a surface plasmon resonance screen of 288 compounds wherein the binding of 4-morpholinoaniline to SipD, 3-indoleacetic acid to SipB, and 5-hydroxyindole to both SipD and SipB were identified. We also identified by NMR the SipD surfaces involved in binding. These three compounds represent a new class of molecules that can bind to T3SS tip (SipD) and translocon (SipB) proteins that could find use in future drug design.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Ave., Lawrence, KS, 66045, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: McShan
authors.affiliation: Biomolecular NMR Core Facility, University of Kansas, Lawrence, KS, 66045, USA.
authors.forename: Asokan
authors.initials: A
authors.lastname: Anbanandam
authors.affiliation: Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Ave., Lawrence, KS, 66045, USA.
authors.forename: Sikta
authors.initials: S
authors.lastname: Patnaik
authors.affiliation: Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Ave., Lawrence, KS, 66045, USA. rdguzman@ku.edu.
authors.forename: Roberto N
authors.identifier: 0000-0003-1172-2917
authors.initials: RN
authors.lastname: De Guzman
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry / Q000378:metabolism*; D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D007210:Indoleacetic Acids / Q000737:chemistry / Q000378:metabolism*; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D012475:Salmonella / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D000069296:Type III Secretion Systems / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000814:Aniline Compounds; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007210:Indoleacetic Acids; D007211:Indoles; D008565:Membrane Proteins; C107188:SspD protein, Salmonella typhimurium; D000069296:Type III Secretion Systems; C094579:invasion protein B, Salmonella typhimurium; C026785:5-hydroxyindole; C030737:indoleacetic acid; C023650:aniline
keywords: STD NMR; SipB; SipD; antibiotics; surface plasmon resonance; translocon; type III secretion system