Association of NMT2 with the acyl-CoA carrier ACBD6 protects the N-myristoyltransferase reaction from palmitoyl-CoA
| Autor: | Frans A. Kuypers, Derek Wang, Joseph L. DeRisi, Giselle M. Knudsen, Joseph Kao, Daniel H. Cheng, Eric Soupene, Alexander L. Greninger |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Biochemistry & Molecular Biology Stereochemistry Coenzyme A Acylation binding protein QD415-436 coenzyme A Medical Biochemistry and Metabolomics Biochemistry Myristic Acid Substrate Specificity 03 medical and health sciences chemistry.chemical_compound Protein acylation Membrane Lipids Endocrinology Humans Protein Interaction Domains and Motifs N-myristoyltransferase 2 protein interaction protein acylation Phospholipids Research Articles phospholipids chemistry.chemical_classification 030102 biochemistry & molecular biology Palmitoyl Coenzyme A Chemistry Binding protein Fatty Acids NMT2 food and beverages Cell Biology Ligand (biochemistry) Enzyme binding 030104 developmental biology Enzyme membranes lipids (amino acids peptides and proteins) ATP-Binding Cassette Transporters Acyl Coenzyme A Biochemistry and Cell Biology Carrier Proteins Acyltransferases Binding domain |
| Zdroj: | Journal of lipid research, vol 57, iss 2 Journal of Lipid Research, Vol 57, Iss 2, Pp 288-298 (2016) |
| Popis: | The covalent attachment of a 14-carbon aliphatic tail on a glycine residue of nascent translated peptide chains is catalyzed in human cells by two N-myristoyltransferase (NMT) enzymes using the rare myristoyl-CoA (C(14)-CoA) molecule as fatty acid donor. Although, NMT enzymes can only transfer a myristate group, they lack specificity for C(14)-CoA and can also bind the far more abundant palmitoyl-CoA (C(16)-CoA) molecule. We determined that the acyl-CoA binding protein, acyl-CoA binding domain (ACBD)6, stimulated the NMT reaction of NMT2. This stimulatory effect required interaction between ACBD6 and NMT2, and was enhanced by binding of ACBD6 to its ligand, C(18:2)-CoA. ACBD6 also interacted with the second human NMT enzyme, NMT1. The presence of ACBD6 prevented competition of the NMT reaction by C(16)-CoA. Mutants of ACBD6 that were either deficient in ligand binding to the N-terminal ACBD or unable to interact with NMT2 did not stimulate activity of NMT2, nor could they protect the enzyme from utilizing the competitor C(16)-CoA. These results indicate that ACBD6 can locally sequester C(16)-CoA and prevent its access to the enzyme binding site via interaction with NMT2. Thus, the ligand binding properties of the NMT/ACBD6 complex can explain how the NMT reaction can proceed in the presence of the very abundant competitive substrate, C(16)-CoA. |
| Databáze: | OpenAIRE |
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