InterPro domain: IPR000182

The N-acetyltransferases (NAT) (EC 2.3.1.-) are enzymes that use acetyl coenzyme A (CoA) to transfer an acetyl group to a substrate, a reactionimplicated in various functions from bacterial antibiotic resistance to mammalian circadian rhythm and chromatin remodeling. The Gcn5-related N-acetyltransferases (GNAT) catalyze the transfer of the acetyl from the CoA donor to a primary amine of the acceptor. The GNAT proteins share a domain composed of four conserved sequence motifs A-D [ 1 , 2 ]. This GNAT domain is named after yeast GCN5 (from General Control Nonrepressed) and related histone acetyltransferases (HATs) like Hat1 and PCAF. HATs acetylate lysine residues of N-terminal histone tails, resulting in transcription activation. Another category of GNAT, the aminoglycoside N-acetyltransferases, confer antibiotic resistance by catalyzing the acetylation of amino groups in aminoglycoside antibiotics [ 3 ]. GNAT proteins can also have anabolic and catabolic functions in both prokaryotes and eukaryotes [ 4 , 4 , 4 , 4 , 5 ].

The acetyltransferase/GNAT domain forms a structurally conserved fold of 6 to 7 beta strands (B) and 4 helices (H) in the topology B1-H1-H2-B2-B3-B4-H3-B5-H4-B6, followed by a C-terminal strand which may be from the same monomer or contributed by another [ 6 , 6 ]. Motifs D (B2-B3), A (B4-H3) and B (B5-H4) are collectively called the HAT core [ 6 , 6 , 6 ], while the N-terminal motif C (B1-H1) is less conserved.

Some proteins known to contain a GNAT domain:

• Yeast GCN5 and Hat1, which are histone acetyltransferases (EC 2.3.1.48).
• Human PCAF, a histone acetyltransferase.
• Mammalian serotonin N-acetyltransferase (SNAT) or arylalkylamine NAT (AANAT), which acetylates serotonin into a circadian neurohormone that may participate in light-dark rhythms, and human mood and behavior.
• Mammalian glucosamine 6-phosphate N-acetyltransferase (GNA1) (EC 2.3.1.4).
• Escherichia coli rimI and rimJ, which acetylate the N-terminal alanine of ribosomal proteins S18 and S5, respectively (EC 2.3.1.128).
• Mycobacterium tuberculosis aminoglycoside 2'-N-acetyltransferase (aac), which acetylates the 2' hydroxyl or amino group of a broad spectrum of aminoglycoside antibiotics.
• Bacillus subtilis bltD and paiA, which acetylate spermine and spermidine.

This entry represents the entire GNAT domain.

1. GCN5-related histone N-acetyltransferases belong to a diverse superfamily that includes the yeast SPT10 protein. Trends Biochem. Sci. 22, 154-5
2. GCN5-related N-acetyltransferases: a structural overview. Arch. Biochem. Biophys. 29, 81-103
3. X-ray structure of the AAC(6')-Ii antibiotic resistance enzyme at 1.8 A resolution; examination of oligomeric arrangements in GNAT superfamily members. Protein Sci. 12, 426-37
4. Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for beta-lactam acetylation. J. Mol. Biol. 325, 1019-30
5. Structure and functions of the GNAT superfamily of acetyltransferases. null 433, 212-26