Structure of N-myristoyltransferase from Aspergillus fumigatus

• Published in: Acta crystallographica. Section D, Biological crystallography. Vol. 71; no. 4; pp. 754 - 761
• Main Authors: Shimada, Takashi, Suzuki, Makoto, Katakura, Shin-ichi
• Format: Journal Article
• Language: English
• Published: 5 Abbey Square, Chester, Cheshire CH1 2HU, England International Union of Crystallography 01.04.2015; Wiley Subscription Services, Inc
• Subjects: Acyl Coenzyme A - metabolism; Acyltransferases - antagonists & inhibitors; Acyltransferases - chemistry; Acyltransferases - metabolism; Amino Acid Sequence; Analogue; Aspergillus; Aspergillus fumigatus; Aspergillus fumigatus - chemistry; Aspergillus fumigatus - enzymology; Aspergillus fumigatus - metabolism; Crystal structure; Crystallography, X-Ray; Drugs; Enzymes; Fatty acids; Glycine; Inhibitors; Models, Molecular; Molecular Sequence Data; N-myristoyltransferase; Proteins; Saccharomyces cerevisiae; Sequence Alignment; Aspergillus fumigatus; N-myristoyltransferase
• ISSN: 1399-0047; 0907-4449; 1399-0047
• DOI: 10.1107/S1399004715000401

N‐Myristoyltransferase (NMT) is an enzyme which translocates the 14‐carbon saturated fatty acid myristate from myristoyl‐CoA to the N‐terminal glycine of substrate peptides. This myristoylation process is involved in protein modification in various eukaryotes, including animals and fungi. Furthermore, this enzyme has been shown to be essential to the growth of various species, such as Saccharomyces cerevisiae, which indicates that NMT is an attractive target for the development of a novel antifungal drug. In this study, the crystal structure of a ternary complex of NMT from Aspergillus fumigatus with S‐(2‐oxo)pentadecyl‐CoA, a myristoyl‐CoA analogue cofactor, and a synthetic inhibitor is reported at a resolution of 2.1 Å. The results advance the understanding of the specificity of NMT inhibitors and provide valuable information for structure‐based drug design.