Journal Article

PUBDB-2025-02331

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The molecular basis for acetylhistidine synthesis by HisAT/NAT16

Myllykoski, M. (Corresponding author)Extern*EMBL* ; Lundekvam, M. ; Osberg, C. ; Nilsen, S. S. ; Arnesen, T. (Corresponding author)Extern*

2025
Springer Nature [London]

This record in other databases:      

Please use a persistent id in citations: doi:10.1038/s41467-025-61145-x  doi:10.3204/PUBDB-2025-02331

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.

---

Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
2. NterAct - Discovery and functional significance of post-translational N-terminal acetylation (772039) (772039)
3. Q-Room - Q-Room – Quintetto’s Holographic Telepresence Room (673617) (673617)
4. FS-Proposal: BAG-20190768 EC (BAG-20190768-EC) (BAG-20190768-EC)
5. FS-Proposal: BAG-20211049 EC (BAG-20211049-EC) (BAG-20211049-EC)

Experiment(s):

1. PETRA Beamline P11 (PETRA III)
2. PETRA Beamline P14 (PETRA III)

Appears in the scientific report 2025

---

Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---