9EMO

Crystal structure of Histidine acetyltransferase with L-arginine and coenzyme A disulfide

9EMO の概要

• エントリーDOI: 10.2210/pdb9emo/pdb
• 関連するPDBエントリー: 9EMD
• 分子名称: Probable N-acetyltransferase 16, [[(2~{S},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-4-oxidanyl-3-phosphonooxy-oxolan-2-yl]methoxy-oxidanyl-phosphoryl] [(3~{R})-4-[[3-[2-[2-[3-[[(2~{R})-4-[[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-4-oxidanyl-3-phosphonooxy-oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxy-3,3-dimethyl-2-oxidanyl-butanoyl]amino]propanoylamino]ethyldisulfanyl]ethylamino]-3-oxidanylidene-propyl]amino]-2,2-dimethyl-3-oxidanyl-4-oxidanylidene-butyl] hydrogen phosphate, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: acyltransferase, gnat fold, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38951.90

構造登録者

Myllykoski, M.,Arnesen, T. (登録日: 2024-03-09, 公開日: 2025-03-19, 最終更新日: 2025-07-16)

主引用文献

Myllykoski, M.,Lundekvam, M.,Osberg, C.,Nilsen, S.S.,Arnesen, T.
The molecular basis for acetylhistidine synthesis by HisAT/NAT16.
Nat Commun, 16:5960-5960, 2025

PubMed Abstract: Acetylhistidine has been detected in human blood, but its origin and function are not known. It is formed when the acetyl group of acetyl-CoA is transferred to the α-amino group of histidine. Here we identify the intracellular NAT16 as the human histidine acetyltransferase (HisAT) responsible for histidine acetylation in vitro and in vivo. A NAT16 variant (p.Phe63Ser) present in over 5% of the population was previously found to correlate with reduced plasma levels of acetylhistidine and increased risk of kidney disease. Our biochemical analysis of HisAT/NAT16 Phe63Ser shows reduced affinity for Histidine supporting a model where this variant has less acetylhistidine catalysis leading to lower blood level of acetylhistidine. We find that HisAT adopts a double-GNAT (Gcn5-related N-Acetyltransferase) fold where the N-terminal domain binds acetyl-CoA and with distinct active site conformation allowing the binding of histidine in between the two domains. We detect similar structures from across living organisms and find that the HisAT structure is conserved in several archaeal and bacterial species. In sum, NAT16 is the human histidine acetyltransferase utilizing a rare double-GNAT structure to steer plasma acetylhistidine levels with potential impact for kidney function.

PubMed: 40595645
DOI: 10.1038/s41467-025-61145-x

実験手法

X-RAY DIFFRACTION (1.9 Å)