1IYK

Crystal structure of candida albicans N-myristoyltransferase with myristoyl-COA and peptidic inhibitor

Summary for 1IYK

• Entry DOI: 10.2210/pdb1iyk/pdb
• Related: 1IYL
• Descriptor: MYRISTOYL-COA:PROTEIN N-MYRISTOYLTRANSFERASE, TETRADECANOYL-COA, [CYCLOHEXYLETHYL]-[[[[4-[2-METHYL-1-IMIDAZOLYL-BUTYL]PHENYL]ACETYL]-SERYL]-LYSINYL]-AMINE, ... (4 entities in total)
• Functional Keywords: transferase
• Biological source: Candida albicans
• Cellular location: Cytoplasm: P30418
• Total number of polymer chains: 2
• Total formula weight: 93992.52

Authors

Sogabe, S.,Fukami, T.A.,Morikami, K.,Shiratori, Y.,Aoki, Y.,D'Arcy, A.,Winkler, F.K.,Banner, D.W.,Ohtsuka, T. (deposition date: 2002-08-29, release date: 2002-12-30, Last modification date: 2023-12-27)

Primary citation

Sogabe, S.,Masubuchi, M.,Sakata, K.,Fukami, T.A.,Morikami, K.,Shiratori, Y.,Ebiike, H.,Kawasaki, K.,Aoki, Y.,Shimma, N.,D'Arcy, A.,Winkler, F.K.,Banner, D.W.,Ohtsuka, T.
Crystal Structures of Candida albicans N-Myristoyltransferase with Two Distinct Inhibitors
CHEM.BIOL., 9:1119-1128, 2002

PubMed Abstract: Myristoyl-CoA:protein N-myristoyltransferase (Nmt) is a monomeric enzyme that catalyzes the transfer of the fatty acid myristate from myristoyl-CoA to the N-terminal glycine residue of a variety of eukaryotic and viral proteins. Genetic and biochemical studies have established that Nmt is an attractive target for antifungal drugs. We present here crystal structures of C. albicans Nmt complexed with two classes of inhibitor competitive for peptide substrates. One is a peptidic inhibitor designed from the peptide substrate; the other is a nonpeptidic inhibitor having a benzofuran core. Both inhibitors are bound into the same binding groove, generated by some structural rearrangements of the enzyme, with the peptidic inhibitor showing a substrate-like binding mode and the nonpeptidic inhibitor binding differently. Further, site-directed mutagenesis for C. albicans Nmt has been utilized in order to define explicitly which amino acids are critical for inhibitor binding. The results suggest that the enzyme has some degree of flexibility for substrate binding and provide valuable information for inhibitor design.

PubMed: 12401496
DOI: 10.1016/S1074-5521(02)00240-5

Experimental method

X-RAY DIFFRACTION (2.3 Å)