6ZMP

Crystal structure of Chaetomium thermophilum Naa20 in complex with a bisubstrate analogue

Summary for 6ZMP

• Entry DOI: 10.2210/pdb6zmp/pdb
• Descriptor: N-terminal acetyltransferase-like protein, CMC-MET-ASP-GLU-LEU, CARBOXYMETHYL COENZYME *A, ... (4 entities in total)
• Functional Keywords: n-terminal acetyltransferase, gnat, catalytic subunit, cytosolic protein
• Biological source: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719); More
• Total number of polymer chains: 4
• Total formula weight: 48620.07

Authors

Layer, D.,Kopp, J.,Sinning, I. (deposition date: 2020-07-03, release date: 2020-12-23, Last modification date: 2024-11-13)

Primary citation

Layer, D.,Kopp, J.,Fontanillo, M.,Kohn, M.,Lapouge, K.,Sinning, I.
Structural basis of Naa20 activity towards a canonical NatB substrate.
Commun Biol, 4:2-2, 2021

PubMed Abstract: N-terminal acetylation is one of the most common protein modifications in eukaryotes and is carried out by N-terminal acetyltransferases (NATs). It plays important roles in protein homeostasis, localization, and interactions and is linked to various human diseases. NatB, one of the major co-translationally active NATs, is composed of the catalytic subunit Naa20 and the auxiliary subunit Naa25, and acetylates about 20% of the proteome. Here we show that NatB substrate specificity and catalytic mechanism are conserved among eukaryotes, and that Naa20 alone is able to acetylate NatB substrates in vitro. We show that Naa25 increases the Naa20 substrate affinity, and identify residues important for peptide binding and acetylation activity. We present the first Naa20 crystal structure in complex with the competitive inhibitor CoA-Ac-MDEL. Our findings demonstrate how Naa20 binds its substrates in the absence of Naa25 and support prospective endeavors to derive specific NAT inhibitors for drug development.

PubMed: 33398031
DOI: 10.1038/s42003-020-01546-4

Experimental method

X-RAY DIFFRACTION (1.57 Å)