Acetyltransferase

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Chemical structure of an acetyl group bound to the remainder R of a molecule. Acetyl.svg
Chemical structure of an acetyl group bound to the remainder R of a molecule.

Acetyltransferase (or transacetylase) is a type of transferase enzyme that transfers an acetyl group, through a process called acetylation. Acetylation serves as a modification that can profoundly transform the functionality of a protein by modifying various properties like hydrophobicity, solubility, and surface attributes. [1] These alterations have the potential to influence the protein's conformation and its interactions with substrates, cofactors, and other macromolecules. [1] The image to the right shows the basic structure of an acetyl group, where R is a variable indicates the remainder of the molecule to which the acetyl group is attached.

Contents

Table 1: Classification of acetyltransferases in human
AcetyltransferasesSubstrateGeneChromosome LocationGene GroupAbbreviation
Histone AcetyltransferaseLysine residues on histones [1] HAT1 [2] 2q31.1 [2] Lysine acetyltransferases [2] HAT
Choline AcetyltransferaseCholine [3] CHAT [4] 10q11.23 [4] NAChAT [3]
Serotonin N-AcetyltransferaseSerotoninAANAT [5] 17q25.1 [5] GCN5 Related N-Acetyltransferases [5] AANAT [5]
NatA AcetyltransferaseN-terminus of various proteins as they emerge from the ribosomeNAA15 [6] 4q31.1 [6] Armadillo like helical domain containing

N-alpha-acetyltransferase subunits [6]

NatA [6]
NatB AcetyltransferasePeptides starting with Met-Asp/Glu/Asn/Gln [7] NAA25 [8] 12q24.13 [8] N-alpha-acetyltransferase subunits

MicroRNA protein coding host genes [8]

NatB [8]

Structure

The 3D structure predictions of histone, choline, and serotonin acetyltransferases are shown to the side of this page. The 3D structure of these proteins are essential for interactions between them and their substrates. Alterations to the 3D structures of these enzymes could result in the chemical modifications not being completed.

Additional examples include:

See also

Related Research Articles

<span class="mw-page-title-main">Histone acetyltransferase</span> Enzymes that catalyze acyl group transfer from acetyl-CoA to histones

Histone acetyltransferases (HATs) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-N-acetyllysine. DNA is wrapped around histones, and, by transferring an acetyl group to the histones, genes can be turned on and off. In general, histone acetylation increases gene expression.

<span class="mw-page-title-main">Choline acetyltransferase</span> Protein-coding gene in the species Homo sapiens

Choline acetyltransferase is a transferase enzyme responsible for the synthesis of the neurotransmitter acetylcholine. ChAT catalyzes the transfer of an acetyl group from the coenzyme acetyl-CoA to choline, yielding acetylcholine (ACh). ChAT is found in high concentration in cholinergic neurons, both in the central nervous system (CNS) and peripheral nervous system (PNS). As with most nerve terminal proteins, ChAT is produced in the body of the neuron and is transported to the nerve terminal, where its concentration is highest. Presence of ChAT in a nerve cell classifies this cell as a "cholinergic" neuron. In humans, the choline acetyltransferase enzyme is encoded by the CHAT gene.

<span class="mw-page-title-main">N-acetyltransferase</span> Class of enzymes

N-acetyltransferase (NAT) is an enzyme that catalyzes the transfer of acetyl groups from acetyl-CoA to arylamines, arylhydroxylamines and arylhydrazines. They have wide specificity for aromatic amines, particularly serotonin, and can also catalyze acetyl transfer between arylamines without CoA. N-acetyltransferases are cytosolic enzymes found in the liver and many tissues of most mammalian species, except the dog and fox, which cannot acetylate xenobiotics.

Aralkylamine <i>N</i>-acetyltransferase Class of enzymes

Aralkylamine N-acetyltransferase (AANAT), also known as arylalkylamine N-acetyltransferase or serotonin N-acetyltransferase (SNAT), is an enzyme that is involved in the day/night rhythmic production of melatonin, by modification of serotonin. It is in humans encoded by the ~2.5 kb AANAT gene containing four exons, located on chromosome 17q25. The gene is translated into a 23 kDa large enzyme. It is well conserved through evolution and the human form of the protein is 80 percent identical to sheep and rat AANAT. It is an acetyl-CoA-dependent enzyme of the GCN5-related family of N-acetyltransferases (GNATs). It may contribute to multifactorial genetic diseases such as altered behavior in sleep/wake cycle and research is on-going with the aim of developing drugs that regulate AANAT function.

<span class="mw-page-title-main">Histone acetylation and deacetylation</span>

Histone acetylation and deacetylation are the processes by which the lysine residues within the N-terminal tail protruding from the histone core of the nucleosome are acetylated and deacetylated as part of gene regulation.

<span class="mw-page-title-main">KAT2A</span> Protein-coding gene in the species Homo sapiens

Histone acetyltransferase KAT2A is an enzyme that in humans is encoded by the KAT2A gene.

<span class="mw-page-title-main">Glucosamine-phosphate N-acetyltransferase</span>

In enzymology, glucosamine-phosphate N-acetyltransferase (GNA) is an enzyme that catalyzes the transfer of an acetyl group from acetyl-CoA to the primary amine in glucosamide-6-phosphate, generating a free CoA and N-acetyl-D-glucosamine-6-phosphate.

<span class="mw-page-title-main">N-alpha-acetyltransferase 10</span> Protein-coding gene in the species Homo sapiens

N-alpha-acetyltransferase 10 (NAA10) also known as NatA catalytic subunit Naa10 and arrest-defective protein 1 homolog A (ARD1A) is an enzyme subunit that in humans is encoded NAA10 gene. Together with its auxiliary subunit Naa15, Naa10 constitutes the NatA complex that specifically catalyzes the transfer of an acetyl group from acetyl-CoA to the N-terminal primary amino group of certain proteins. In higher eukaryotes, 5 other N-acetyltransferase (NAT) complexes, NatB-NatF, have been described that differ both in substrate specificity and subunit composition.

<span class="mw-page-title-main">KAT7 (gene)</span> Protein-coding gene in the species Homo sapiens

Histone acetyltransferase KAT7 is an enzyme that in humans is encoded by the KAT7 gene. It specifically acetylates H4 histones at the lysine12 residue (H4K12) and is necessary for origin licensing and DNA replication. KAT7 associates with origins of replication during G1 phase of the cell cycle through complexing with CDT1. Geminin is thought to inhibit the acetyltransferase activity of KAT7 when KAT7 and CDT1 are complexed together.

Protein acetylation are acetylation reactions that occur within living cells as drug metabolism, by enzymes in the liver and other organs. Pharmaceuticals frequently employ acetylation to enable such esters to cross the blood–brain barrier, where they are deacetylated by enzymes (carboxylesterases) in a manner similar to acetylcholine. Examples of acetylated pharmaceuticals are diacetylmorphine (heroin), acetylsalicylic acid (aspirin), THC-O-acetate, and diacerein. Conversely, drugs such as isoniazid are acetylated within the liver during drug metabolism. A drug that depends on such metabolic transformations in order to act is termed a prodrug.

H3K27ac is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates acetylation of the lysine residue at N-terminal position 27 of the histone H3 protein.

H4K16ac is an epigenetic modification to the DNA packaging protein Histone H4. It is a mark that indicates the acetylation at the 16th lysine residue of the histone H4 protein.

H4K5ac is an epigenetic modification to the DNA packaging protein histone H4. It is a mark that indicates the acetylation at the 5th lysine residue of the histone H4 protein. H4K5 is the closest lysine residue to the N-terminal tail of histone H4. It is enriched at the transcription start site (TSS) and along gene bodies. Acetylation of histone H4K5 and H4K12ac is enriched at centromeres.

H4K8ac, representing an epigenetic modification to the DNA packaging protein histone H4, is a mark indicating the acetylation at the 8th lysine residue of the histone H4 protein. It has been implicated in the prevalence of malaria.

H4K12ac is an epigenetic modification to the DNA packaging protein histone H4. It is a mark that indicates the acetylation at the 12th lysine residue of the histone H4 protein. H4K12ac is involved in learning and memory. It is possible that restoring this modification could reduce age-related decline in memory.

H4K91ac is an epigenetic modification to the DNA packaging protein histone H4. It is a mark that indicates the acetylation at the 91st lysine residue of the histone H4 protein. No known diseases are attributed to this mark but it might be implicated in melanoma.

H3K14ac is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the acetylation at the 14th lysine residue of the histone H3 protein.

H3K9ac is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the acetylation at the 9th lysine residue of the histone H3 protein.

H3K36ac is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the acetylation at the 36th lysine residue of the histone H3 protein.

H3K56ac is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the acetylation at the 56th lysine residue of the histone H3 protein.

References

  1. 1 2 3 Marmorstein R, Zhou MM (July 2014). "Writers and readers of histone acetylation: structure, mechanism, and inhibition". Cold Spring Harbor Perspectives in Biology. 6 (7): a018762. doi:10.1101/cshperspect.a018762. PMC   4067988 . PMID   24984779.
  2. 1 2 3 Verreault A, Kaufman PD, Kobayashi R, Stillman B (January 1998). "Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1 acetyltransferase". Current Biology. 8 (2): 96–108. doi: 10.1016/s0960-9822(98)70040-5 . PMID   9427644. S2CID   201273.
  3. 1 2 Kim AR, Rylett RJ, Shilton BH (December 2006). "Substrate binding and catalytic mechanism of human choline acetyltransferase". Biochemistry. 45 (49): 14621–14631. doi:10.1021/bi061536l. PMID   17144655.
  4. 1 2 Strauss WL, Kemper RR, Jayakar P, Kong CF, Hersh LB, Hilt DC, Rabin M (February 1991). "Human choline acetyltransferase gene maps to region 10q11-q22.2 by in situ hybridization". Genomics. 9 (2): 396–398. doi: 10.1016/0888-7543(91)90273-H . PMID   1840566.
  5. 1 2 3 4 Coon SL, Mazuruk K, Bernard M, Roseboom PH, Klein DC, Rodriguez IR (May 1996). "The human serotonin N-acetyltransferase (EC 2.3.1.87) gene (AANAT): structure, chromosomal localization, and tissue expression". Genomics. 34 (1): 76–84. doi:10.1006/geno.1996.0243. PMID   8661026.
  6. 1 2 3 4 Arnesen T, Van Damme P, Polevoda B, Helsens K, Evjenth R, Colaert N, et al. (May 2009). "Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans". Proceedings of the National Academy of Sciences of the United States of America. 106 (20): 8157–8162. Bibcode:2009PNAS..106.8157A. doi: 10.1073/pnas.0901931106 . PMC   2688859 . PMID   19420222.
  7. ↑ Hong H, Cai Y, Zhang S, Ding H, Wang H, Han A (April 2017). "Molecular Basis of Substrate Specific Acetylation by N-Terminal Acetyltransferase NatB". Structure. 25 (4): 641–649.e3. doi: 10.1016/j.str.2017.03.003 . PMID   28380339.
  8. 1 2 3 4 Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, et al. (July 2012). "N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB". Proceedings of the National Academy of Sciences of the United States of America. 109 (31): 12449–12454. Bibcode:2012PNAS..10912449V. doi: 10.1073/pnas.1210303109 . PMC   3412031 . PMID   22814378.
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