Document Type

Article

Publication Date

7-2017

Publication Title

FEBS Letters

Volume

591

Issue

15

Pages

2348-2361

Abstract

Gcn5‐related N‐acetyltransferases (GNATs) are found in all kingdoms of life and catalyze important acyl transfer reactions in diverse cellular processes. While many 3D structures of GNATs have been determined, most do not contain acceptor substrates in their active sites. To expand upon existing crystallographic strategies for improving acceptor‐bound GNAT structures, we synthesized peptide substrate analogs and reacted them with CoA in PA4794 protein crystals. We found two separate mechanisms for bisubstrate formation: (a) a novel X‐ray induced radical‐mediated alkylation of CoA with an alkene peptide and (b) direct alkylation of CoA with a halogenated peptide. Our approach is widely applicable across the GNAT superfamily and can be used to improve the success rate of obtaining liganded structures of other acyltransferases.

Comments

Author Posting. © Federation of European Biochemical Societies 2017. This article is posted here by permission of the Federation of European Biochemical Societies for personal use, not for redistribution. The article was published in FEBS Letters, vol. 591, no. 15, 2017, https://doi.org/10.1002/1873-3468.12753.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Available for download on Sunday, July 01, 2018

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