6rxq | pdb_00006rxq
Crystal structure of CobB Ac2 (A76G,I131C,V162A) in complex with H4K16Cr-2'OH-ADPr peptide intermediate after soaking
Structural highlights
FunctionNPD_ECOLI NAD-dependent lysine deacetylase and desuccinylase that specifically removes acetyl and succinyl groups on target proteins. Modulates the activities of several proteins which are inactive in their acylated form. Activates the enzyme acetyl-CoA synthetase by deacetylating 'Lys-609' in the inactive, acetylated form of the enzyme. May also modulate the activity of other propionyl-adenosine monophosphate (AMP)-forming enzymes.[1] [2] [3] Publication Abstract from PubMedLysine acylations, a family of diverse protein modifications varying in acyl group length, charge and saturation, are linked to many important physiological processes. Only a small set of substrate-promiscuous lysine acetyltransferases and deacetylases (KDACs) install and remove this vast variety of modifications. Engineered KDACs that remove only one type of acylation would help to dissect the different contributions of distinct acylations to cell physiology. Therefore, we developed a bacterial selection system for the directed evolution of KDACs with which we identified variants up to 400 times more selective for butyryl- compared to crotonyl-lysine. Structural analyses revealed that the enzyme adopts different conformational states depending on the type of acylation of the bound peptide. We used the butyryl-selective KDAC variant to shift the cellular acylation spectrum towards increased lysine crotonylation. Hence, these new enzymes will help dissecting the different roles of lysine acylations in cell physiology. Evolved, Selective Erasers of Distinct Lysine Acylations.,Spinck M, Neumann-Staubitz P, Ecke M, Gasper R, Neumann H Angew Chem Int Ed Engl. 2020 Mar 18. doi: 10.1002/anie.202002899. PMID:32187803[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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