First NAT-inhibitors developed & first NAT-complex structure solved
First published on UiB.no November 5, 2015
N-terminal acetyltransferases (NATs) catalyse the N-terminal acetylation of a majority of human proteins. The NAT-enzymes have been linked to cancer development and progression, and detailed molecular knowledge is essential for developing specific compounds to target the NATs for potential cancer chemotherapy.
Now, researchers at the NAT-group, MBI, UiB, Department of Surgery, HUS, and the group of Professor Paul R. Thompson at The Scripps Research Institute Florida, have developed the first specific NAT-inhibitors. These inhibitors are able to discriminate between different NAT-enzymes in vitro and are now being further developed for in vivo use (Foyn et al., ACS Chemical Biology, 2013).
Very recently, similar inhibitors were used by Professor Ronen Marmorstein (The Wistar Institute) to solve the first structure of a NAT-complex. The structure of NatA, the major NAT-complex in eukaryotes, revealed the molecular basis for N-terminal acetylation by a NAT and defined interesting aspects on how the catalytic subunit of the complex is modulated by the auxiliary subunit (Liszczak et al., Nature Structural & Molecular Biology, 2013).
Copyright: Thomas Arnesen
Design, Synthesis, and Kinetic Characterization of Protein N-Terminal Acetyltransferase Inhibitors
Foyn H, Jones JE, Lewallen D, Narawane R, Varhaug JE, Thompson PR, Arnesen T.
ACS Chem Biol. 2013;8(6):1121-7.
Molecular basis for N-terminal acetylation by the heterodimeric NatA complex
Liszczak G, Goldberg JM, Foyn H, Petersson EJ, Arnesen T, Marmorstein R.
Nat Struct Mol Biol. 2013 Sep;20(9):1098-105.