Glycylpeptide N-tetradecanoyltransferase

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glycylpeptide N-tetradecanoyltransferase
N-Myristoyltransferase Subunit Bound to Myristoyl-CoA.png
Crystal structure of human type-I N-myristoyltransferase with bound myristoyl-CoA. Myristoyl-CoA (red). PDB ID: 3IU1
Identifiers
EC no. 2.3.1.97
CAS no. 110071-61-9
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
Search
PMC articles
PubMed articles
NCBI proteins
NMT, N-terminal
Identifiers
SymbolNMT
Pfam PF01233
InterPro IPR022676
CATH 3IU1
SCOP2 3IU1 / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
NMT, C-terminal
Identifiers
SymbolNMT_C
Pfam PF02799
InterPro IPR022677
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

In enzymology, a glycylpeptide N-tetradecanoyltransferase (EC 2.3.1.97) is an enzyme that catalyzes the chemical reaction

Contents

tetradecanoyl-CoA + glycylpeptide CoA + N-tetradecanoylglycylpeptide

Thus, the two substrates of this enzyme are tetradecanoyl-CoA and glycylpeptide, whereas its two products are CoA and N-tetradecanoylglycylpeptide. It participates in the N-Myristoylation of proteins, and in vertebrates there are two isoenzymes NMT1 and NMT2.

Besides tetradecanoyl-CoA, this enzyme is also capable of using modified versions of this substrate. [1] In human retina, an even wider range of fatty acids, including 14:1 n–9, 14:2n–6, and 12:0, are accepted by the enzyme and grafted onto guanylate cyclase activators. [2] This is mainly a result of a special set of fatty-acid-CoA substrates available in the retina. [3]

Nomenclature

This enzyme belongs to the family of transferases, specifically those N-acyltransferases transferring groups other than aminoacyl groups (cd04301). The systematic name of this enzyme class is tetradecanoyl-CoA:glycylpeptide N-tetradecanoyltransferase. Other names in common use include peptide N-myristoyltransferase (NMT), myristoyl-CoA-protein N-myristoyltransferase, myristoyl-coenzyme A:protein N-myristoyl transferase, myristoylating enzymes, and protein N-myristoyltransferase.

Structural studies

As of late 2007, 9 structures have been solved for this class of enzymes, with PDB accession codes 1IIC, 1IID, 1IYK, 1IYL, 1RXT, 2NMT, 2P6E, 2P6F, and 2P6G.

The enzyme folds into two domains, each with a double EF-hand arrangement.

Related Research Articles

<span class="mw-page-title-main">Myristoylation</span> Lipidation modification

Myristoylation is a lipidation modification where a myristoyl group, derived from myristic acid, is covalently attached by an amide bond to the alpha-amino group of an N-terminal glycine residue. Myristic acid is a 14-carbon saturated fatty acid (14:0) with the systematic name of n-tetradecanoic acid. This modification can be added either co-translationally or post-translationally. N-myristoyltransferase (NMT) catalyzes the myristic acid addition reaction in the cytoplasm of cells. This lipidation event is the most common type of fatty acylation and is present in many organisms, including animals, plants, fungi, protozoans and viruses. Myristoylation allows for weak protein–protein and protein–lipid interactions and plays an essential role in membrane targeting, protein–protein interactions and functions widely in a variety of signal transduction pathways.

<span class="mw-page-title-main">Long-chain-fatty-acid—CoA ligase</span> Class of enzymes

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<span class="mw-page-title-main">Carnitine palmitoyltransferase I</span> Enzyme found in humans

Carnitine palmitoyltransferase I (CPT1) also known as carnitine acyltransferase I, CPTI, CAT1, CoA:carnitine acyl transferase (CCAT), or palmitoylCoA transferase I, is a mitochondrial enzyme responsible for the formation of acyl carnitines by catalyzing the transfer of the acyl group of a long-chain fatty acyl-CoA from coenzyme A to l-carnitine. The product is often palmitoylcarnitine, but other fatty acids may also be substrates. It is part of a family of enzymes called carnitine acyltransferases. This "preparation" allows for subsequent movement of the acyl carnitine from the cytosol into the intermembrane space of mitochondria.

<span class="mw-page-title-main">Glycylpeptide N-tetradecanoyltransferase 2</span> Protein-coding gene in the species Homo sapiens

Glycylpeptide N-tetradecanoyltransferase 2 known also as N-myristoyltransferase, is an enzyme that in humans is encoded by the NMT2 gene.

In enzymology, an acyl-[acyl-carrier-protein]-phospholipid O-acyltransferase is an enzyme that catalyzes the chemical reaction

In enzymology, a [acyl-carrier-protein] S-acetyltransferase is an enzyme that catalyzes the reversible chemical reaction

In enzymology, a beta-ketoacyl-acyl-carrier-protein synthase I is an enzyme that catalyzes the chemical reaction

In enzymology, a beta-ketoacyl-acyl-carrier-protein synthase II (EC 2.3.1.179) is an enzyme that catalyzes the chemical reaction

In enzymology, a glycerol-3-phosphate O-acyltransferase is an enzyme that catalyzes the chemical reaction

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In enzymology, a long-chain-alcohol O-fatty-acyltransferase is an enzyme that catalyzes the chemical reaction

In enzymology, a mycocerosate synthase (EC 2.3.1.111) is an enzyme that catalyzes the chemical reaction

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<span class="mw-page-title-main">Glycylpeptide N-tetradecanoyltransferase 1</span> Protein-coding gene in the species Homo sapiens

Glycylpeptide N-tetradecanoyltransferase 1 also known as myristoyl-CoA:protein N-myristoyltransferase 1 (NMT-1) is an enzyme that in humans is encoded by the NMT1 gene. It belongs to the protein N-terminal methyltransferase and glycylpeptide N-tetradecanoyltransferase family of enzymes.

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

Glycine-N-acyltransferase, also known as GLYAT, is an enzyme which in humans is encoded by the GLYAT gene.

<span class="mw-page-title-main">1-Lysophosphatidylcholine</span>

1-Lysophosphatidylcholines are a class of phospholipids that are intermediates in the metabolism of lipids. They result from the hydrolysis of an acyl group from the sn-1 position of phosphatidylcholine. They are also called 2-acyl-sn-glycero-3-phosphocholines. The synthesis of phosphatidylcholines with specific fatty acids occurs through the synthesis of 1-lysoPC. The formation of various other lipids generates 1-lysoPC as a by-product.

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

Ghrelin O-acyltransferase also known as membrane bound O-acyltransferase domain containing 4 is an enzyme that in humans is encoded by the MBOAT4 gene. It is homologous to other membrane-bound O-acyltransferases. It is a polytopic membrane protein what takes part in lipid signaling reactions. It is the only known enzyme that catalyzes the acylation of ghrelin through the transfer of n-octanoic acid to ghrelin Ser3. Ghrelin O-acyltransferase function is essential in regulation of appetite and the release of growth hormone. Ghrelin O-acyltransferase is a target for scientific research due to promising applications in the treatment of diabetes, eating disorders, and metabolic diseases.

References

  1. Heuckeroth RO, Towler DA, Adams SP, Glaser L, Gordon JI (1988). "11-(Ethylthio)undecanoic acid. A myristic acid analogue of altered hydrophobicity which is functional for peptide N-myristoylation with wheat germ and yeast acyltransferase". J. Biol. Chem. 263 (5): 2127–33. doi: 10.1016/S0021-9258(18)69180-X . PMID   3123489.
  2. Rundle, Dana R.; Rajala, Raju V.S.; Anderson, Robert E. (July 2002). "Characterization of Type I and Type II Myristoyl-CoA:protein N -Myristoyltransferases with the Acyl-CoAs found on Heterogeneously Acylated Retinal Proteins". Experimental Eye Research. 75 (1): 87–97. doi:10.1006/exer.2002.1189. PMID   12123640.
  3. Bereta, G; Palczewski, K (10 May 2011). "Heterogeneous N-terminal acylation of retinal proteins results from the retina's unusual lipid metabolism". Biochemistry. 50 (18): 3764–76. doi:10.1021/bi200245t. PMC   3086940 . PMID   21449552.