1IYL

Crystal Structure of Candida albicans N-myristoyltransferase with Non-peptidic Inhibitor

1IYL の概要

• エントリーDOI: 10.2210/pdb1iyl/pdb
• 関連するPDBエントリー: 1IYK
• 分子名称: Myristoyl-CoA:Protein N-Myristoyltransferase, (1-METHYL-1H-IMIDAZOL-2-YL)-(3-METHYL-4-{3-[(PYRIDIN-3-YLMETHYL)-AMINO]-PROPOXY}-BENZOFURAN-2-YL)-METHANONE (2 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Candida albicans
• 細胞内の位置: Cytoplasm: P30418
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 182899.65

構造登録者

Sogabe, S.,Fukami, T.A.,Morikami, K.,Shiratori, Y.,Aoki, Y.,D'Arcy, A.,Winkler, F.K.,Banner, D.W.,Ohtsuka, T. (登録日: 2002-08-29, 公開日: 2002-12-30, 最終更新日: 2023-10-25)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.2 Å)