This entry represents the N-terminal half of the structure of histone acetyl transferase HAT1. It is often found in association with the C-terminal part of . It seems to be motifs C and D of the structure. Histone acetyltransferases (HATs) catalyse the transfer of an acetyl group from acetyl-CoA to the lysine E-amino groups on the N-terminal tails of histones. HATs are involved in transcription since histones tend to be hyper-acetylated in actively transcribed regions of chromatin, whereas in transcriptionally silent regions histones are hypo-acetylated [].
This entry represents the catalytic subunit of histone acetyltransferase type B () (also known as HAT1), which is the catalytic component of the histone acetylase B (HAT-B) complex [, , ]. The HAT-B complex is composed of at least HAT1 and HAT2. In the cytoplasm, this complex binds to the histone H4 tail. In the nucleus, the HAT-B complex has an additional component, the histone H3/H4 chaperone HIF1.This enzyme acetylates soluble but not nucleosomal H4 at Lys-12, which is required for telomeric silencing. HAT1 has intrinsic substrate specificity that modifies lysine in recognition sequence GXGKXG. It is involved in DNA double-strand break repair [].
Histone acetylation is carried out by a class of enzymes known as histone acetyltransferases (HATs), which catalyse the transfer of an acetyl group from acetyl-CoA to the lysine E-amino groups on the N-terminal tails of histones [, ]. Early indication that HATs were involved in transcription came from the observation that in actively transcribed regions of chromatin, histones tend to be hyperacetylated, whereas in transcriptionally silent regions histones are hypoacetylated. The histone acetyltransferases are divided into five families. These include the Gcn5-related acetyltransferases (GNATs); the MYST (for `MOZ, Ybf2/Sas3, Sas2 and Tip60)-related HATs; p300/CBP HATs; the general transcription factor HATs, which include the TFIID subunit TAF250; and the nuclear hormone-related HATs SRC1 and ACTR (SRC3). The GCN5-related N-acetyltransferase superfamily includes such enzymes as the histone acetyltransferases GCN5 and Hat1, the elongator complex subunit Elp3, the mediator-complex subunit Nut1, and Hpa2 [].Many GNATs share several functional domains, including an N-terminal region of variable length, an acetyltransferase domain that encompasses the conserved sequence motifs described above, a region that interacts with the coactivator Ada2, and a C-terminal bromodomain that is believed to interact with acetyl-lysine residues. Members of the GNAT family are important for the regulation of cell growth and development. In mice, knockouts of Gcn5L are embryonic lethal. Yeast Gcn5 is needed for normal progression through the G2-M boundary and mitotic gene expression. The importance of GNATs is probably related to their role in transcription and DNA repair.The yeast GCN5 (yGCN5) transcriptional coactivator functions as a histone acetyltransferase (HAT) to promote transcriptional activation. The crystal structure of the yeast histone acetyltransferase Hat1-acetyl coenzyme A (AcCoA) shows that Hat1 has an elongated, curved structure, and the AcCoA molecule is bound in a cleft on the concave surface of the protein, marking the active site of the enzyme. A channel of variable width and depth that runs across the protein is probably the binding site for the histone substrate []. The central protein core associated with AcCoA binding that appears to be structurally conserved among a superfamily of N-acetyltransferases, including yeast histone acetyltransferase 1 and Serratia marcescens aminoglycoside 3-N-acetyltransferase [].This entry represents the C-terminal region of histone acetyltransferase type B () (also known as HAT1) from fungi and metazoa, which is required for telomeric silencing and has intrinsic substrate specificity that modifies lysine in recognition sequence GXGKXG. It is also involved in DNA double-strand break repair. The structure from human HAT1 revealed that this domain consists of a bundle of helices with one short β-strand [].
The N-acetyltransferases (NAT) (EC 2.3.1.-) are enzymes that use acetylcoenzyme A (CoA) to transfer an acetyl group to a substrate, a reactionimplicated in various functions from bacterial antibiotic resistance tomammalian circadian rhythm and chromatin remodeling. The Gcn5-relatedN-acetyltransferases (GNAT) catalyze the transfer of the acetyl from the CoAdonor to a primary amine of the acceptor. The GNAT proteins share a domaincomposed of four conserved sequence motifs A-D [, ]. This GNAT domain isnamed after yeast GCN5 (from General Control Nonrepressed) and related histoneacetyltransferases (HATs) like Hat1 and PCAF. HATs acetylate lysine residuesof amino terminal histone tails, resulting in transcription activation.Another category of GNAT, the aminoglycoside N-acetyltransferases, conferantibiotic resistance by catalyzing the acetylation of amino groups inaminoglycoside antibiotics []. GNAT proteins can also have anabolic andcatabolic functions in both prokaryotes and eukaryotes [, , , , ].The acetyltransferase/GNAT domain forms a structurally conserved fold of 6 to7 beta strands (B) and 4 helices (H) in the topologyB1-H1-H2-B2-B3-B4-H3-B5-H4-B6, followed by a C-terminal strand which may befrom the same monomer or contributed by another [, ]. MotifsD (B2-B3), A (B4-H3) and B (B5-H4) are collectively called the HAT core[, , ], while the N-terminal motif C (B1-H1) is less conserved.This entry represents the vertebrate-likeNAGS-type GNAT domain [].
The N-acetyltransferases (NAT) ([intenz:2.3.1.-]) are enzymes that use acetyl coenzyme A (CoA) to transfer an acetyl group to a substrate, a reaction implicated in various functions from bacterial antibiotic resistance to mammalian circadian rhythm and chromatin remodeling. The Gcn5-related N-acetyltransferases (GNAT) catalyse 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 [, ]. This GNAT domain is named after yeast GCN5 (from General Control Nonrepressed) and related histone acetyltransferases (HATs) like Hat1 and PCAF. HATs acetylate lysine residuesof amino terminal histone tails, resulting in transcription activation. Another category of GNAT, the aminoglycoside N-acetyltransferases, confer antibiotic resistance by catalysing the acetylation of amino groups in aminoglycoside antibiotics []. GNAT proteins can also have anabolic and catabolic functions in both prokaryotes and eukaryotes [, , , , ].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 [, ]. MotifsD (B2-B3), A (B4-H3) and B (B5-H4) are collectively called the HAT core [, , ], while the N-terminal motif C (B1-H1) is less conserved.The entry represents the NAGS-type GNAT domain [, ].
The N-acetyltransferases (NAT) ([intenz:2.3.1.-]) are enzymes that use acetyl coenzyme A (CoA) to transfer an acetyl group to a substrate, a reaction implicated in various functions from bacterial antibiotic resistance to mammalian circadian rhythm and chromatin remodelling. The Gcn5-related N-acetyltransferases (GNAT) catalyse 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 [, ]. 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 catalysing the acetylation of amino groups in aminoglycoside antibiotics []. GNAT proteins can also have anabolic and catabolic functions in both prokaryotes and eukaryotes [, , , , ].The acetyltransferase/GNAT domain forms a structurally conserved fold of 6 to 7 β-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 [, ]. Motifs D (B2-B3), A (B4-H3) and B (B5-H4) are collectively called the HAT core [, , ], while the N-terminal motif C (B1-H1) is less conserved.Some proteins known to contain a GNAT domain:Actinobacterial mycothiol acetyltransferase (MshD), which catalyses the transfer of acetyl from acetyl-CoA to desacetylmycothiol to form mycothiol. 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 mayparticipate in light-dark rhythms, and human mood and behaviour.Mammalian glucosamine 6-phosphate N-acetyltransferase (GNA1) (EC 2.3.1.4).Escherichia coli RimI and RimJ, which acetylate the N-terminal alanine ofribosomal 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 ofaminoglycoside antibiotics.Bacillus subtilis BltD and PaiA, which acetylate spermine and spermidine.This entry represents the entire GNAT domain.
The N-acetyltransferases (NAT) (EC 2.3.1.-) are enzymes that use acetylcoenzyme A (CoA) to transfer an acetyl group to a substrate, a reactionimplicated in various functions from bacterial antibiotic resistance tomammalian circadian rhythm and chromatin remodeling. The Gcn5-relatedN-acetyltransferases (GNAT) catalyze the transfer of the acetyl from the CoAdonor to a primary amine of the acceptor. The GNAT proteins share a domaincomposed of four conserved sequence motifs A-D [, ]. 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 amino 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 []. GNAT proteins can also have anabolic and catabolic functions in both prokaryotes and eukaryotes [, , , , ].The acetyltransferase/GNAT domain forms a structurally conserved fold of 6 to7 beta strands (B) and 4 helices (H) in the topologyB1-H1-H2-B2-B3-B4-H3-B5-H4-B6, followed by a C-terminal strand which may befrom the same monomer or contributed by another [, ]. MotifsD (B2-B3), A (B4-H3) and B (B5-H4) are collectively called the HAT core[, , ], while the N-terminal motif C (B1-H1) is less conserved.This entry represents the ATAT-type of the GNAT domain []. Proteins containing this domain include alpha-tubulin N-acetyltransferase, originally known as mechanosensory abnormality protein 17 (Mec-17), as it is the protein product of one of the 18 genes required for the development and function of the touch receptor neuron for gentle touch []. Mec-17 specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules []. It is inefficient, and its activity is enhanced when tubulin is incorporated in microtubules []. It may affect microtubule stability and regulate microtubule dynamics.
