Crystal structure of the anti-fungal target N-myristoyl transferase
| Autor: | Eric de La Fortelle, Mark Egerton, Gérard Bricogne, John J. Irwin, Roger Camble, Richard A. Pauptit, Ian W. F. Taylor, Alan Tunnicliffe, Alec D. Tucker, Anil Mistry, Filippo Mancia, Simon A. Weston, Jeremy G. Colls, Gina Rosenbrock |
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| Rok vydání: | 1998 |
| Předmět: |
Models
Molecular Protein Folding Antifungal Agents Xenon Stereochemistry Molecular Sequence Data Molecular Conformation Sequence alignment Biology Crystallography X-Ray Biochemistry Protein Structure Secondary Immunocompromised Host Structural Biology Candida albicans Genetics Transferase Humans Amino Acid Sequence Peptide sequence Myristoylation chemistry.chemical_classification Sequence Homology Amino Acid Candidiasis Fungi Glutamic acid Recombinant Proteins Amino acid Enzyme chemistry Protein folding Acyl Coenzyme A Sequence Alignment Acyltransferases |
| Zdroj: | Nature structural biology. 5(3) |
| ISSN: | 1072-8368 |
| Popis: | N-myristoyl transferase (NMT) catalyzes the transfer of the fatty acid myristate from myristoyl-CoA to the N-terminal glycine of substrate proteins, and is found only in eukaryotic cells. The enzyme in this study is the 451 amino acid protein produced by Candida albicans, a yeast responsible for the majority of systemic infections in immuno-compromised humans. NMT activity is essential for vegetative growth, and the structure was determined in order to assist in the discovery of a selective inhibitor of NMT which could be developed as an anti-fungal drug. NMT has no sequence homology with other protein sequences and has a novel alpha/beta fold which shows internal two-fold symmetry, which may be a result of gene duplication. On one face of the protein there is a long, curved, relatively uncharged groove, at the center of which is a deep pocket. The pocket floor is negatively charged due to the vicinity of the C-terminal carboxylate and a nearby conserved glutamic acid residue, which separates the pocket from a cavity. These observations, considered alongside the positions of residues whose mutation affects substrate binding and activity, suggest that the groove and pocket are the sites of substrate binding and the floor of the pocket is the catalytic center. |
| Databáze: | OpenAIRE |
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