2YNC
Plasmodium vivax N-myristoyltransferase in complex with YnC12-CoA thioester.
Summary for 2YNC
| Entry DOI | 10.2210/pdb2ync/pdb |
| Related | 2YND 2YNE 4A95 4B10 4B11 4B12 4B13 4B14 4BBH |
| Descriptor | GLYCYLPEPTIDE N-TETRADECANOYLTRANSFERASE, DIMETHYL SULFOXIDE, TETRADEC-13-YNOIC ACID - COA THIOESTER, ... (8 entities in total) |
| Functional Keywords | transferase, myristoylation, malaria |
| Biological source | PLASMODIUM VIVAX More |
| Total number of polymer chains | 3 |
| Total formula weight | 138313.41 |
| Authors | Wright, M.H.,Clough, B.,Rackham, M.D.,Brannigan, J.A.,Grainger, M.,Bottrill, A.R.,Heal, W.P.,Broncel, M.,Serwa, R.A.,Mann, D.,Leatherbarrow, R.J.,Wilkinson, A.J.,Holder, A.A.,Tate, E.W. (deposition date: 2012-10-13, release date: 2014-01-15, Last modification date: 2024-05-08) |
| Primary citation | Wright, M.H.,Clough, B.,Rackham, M.D.,Rangachari, K.,Brannigan, J.A.,Grainger, M.,Moss, D.K.,Bottrill, A.R.,Heal, W.P.,Broncel, M.,Serwa, R.A.,Brady, D.,Mann, D.,Leatherbarrow, R.J.,Tewari, R.,Wilkinson, A.J.,Holder, A.A.,Tate, E.W. Validation of N-Myristoyltransferase as an Antimalarial Drug Target Using an Integrated Chemical Biology Approach. Nat.Chem., 6:112-, 2014 Cited by PubMed Abstract: Malaria is an infectious disease caused by parasites of the genus Plasmodium, which leads to approximately one million deaths per annum worldwide. Chemical validation of new antimalarial targets is urgently required in view of rising resistance to current drugs. One such putative target is the enzyme N-myristoyltransferase, which catalyses the attachment of the fatty acid myristate to protein substrates (N-myristoylation). Here, we report an integrated chemical biology approach to explore protein myristoylation in the major human parasite P. falciparum, combining chemical proteomic tools for identification of the myristoylated and glycosylphosphatidylinositol-anchored proteome with selective small-molecule N-myristoyltransferase inhibitors. We demonstrate that N-myristoyltransferase is an essential and chemically tractable target in malaria parasites both in vitro and in vivo, and show that selective inhibition of N-myristoylation leads to catastrophic and irreversible failure to assemble the inner membrane complex, a critical subcellular organelle in the parasite life cycle. Our studies provide the basis for the development of new antimalarials targeting N-myristoyltransferase. PubMed: 24451586DOI: 10.1038/NCHEM.1836 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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