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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.

SUBMITTER: He B

PROVIDER: S-EPMC2789734 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Binding ensemble profiling with photoaffinity labeling (BEProFL) approach: mapping the binding poses of HDAC8 inhibitors.

He Bai B Velaparthi Subash S Pieffet Gilles G Pennington Chris C Mahesh Aruna A Holzle Denise L DL Brunsteiner Michael M van Breemen Richard R Blond Sylvie Y SY Petukhov Pavel A PA

Journal of medicinal chemistry 20091101 22

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 ...[more]

PMID: 19886628

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