title: Binding ensemble profiling with photoaffinity labeling (BEProFL) approach: mapping the binding poses of HDAC8 inhibitors.
abstract: A binding ensemble profiling with (f)photoaffinity labeling (BEProFL) approach that utilizes photolabeling of HDAC8 with a probe containing a UV-activated aromatic azide, mapping of the covalent modifications by liquid chromatography-tandem mass spectrometry, and a computational method to characterize the multiple binding poses of the probe is described. By use of the BEProFL approach, two distinct binding poses of the HDAC8 probe were identified. The data also suggest that an "upside-down" pose with the surface binding group of the probe bound in an alternative pocket near the catalytic site may contribute to the binding.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA.
authors.forename: Bai
authors.initials: B
authors.lastname: He
authors.forename: Subash
authors.initials: S
authors.lastname: Velaparthi
authors.forename: Gilles
authors.initials: G
authors.lastname: Pieffet
authors.forename: Chris
authors.initials: C
authors.lastname: Pennington
authors.forename: Aruna
authors.initials: A
authors.lastname: Mahesh
authors.forename: Denise L
authors.initials: DL
authors.lastname: Holzle
authors.forename: Michael
authors.initials: M
authors.lastname: Brunsteiner
authors.forename: Richard
authors.initials: R
authors.lastname: van Breemen
authors.forename: Sylvie Y
authors.initials: SY
authors.lastname: Blond
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Petukhov
mesh_terms: D000595:Amino Acid Sequence; D001386:Azides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002853:Chromatography, Liquid; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D019920:Photoaffinity Labels / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D001386:Azides; D056572:Histone Deacetylase Inhibitors; D010446:Peptide Fragments; D019920:Photoaffinity Labels; D012097:Repressor Proteins; C409470:HDAC8 protein, human; D006655:Histone Deacetylases