2P6G

Crystal structures of Saccharomyces cerevisiae N-myristoyltransferase with bound myristoyl-CoA and inhibitors

2P6G の概要

• エントリーDOI: 10.2210/pdb2p6g/pdb
• 関連するPDBエントリー: 2P6E 2P6F
• 分子名称: Glycylpeptide N-tetradecanoyltransferase, TETRADECANOYL-COA, 1-(CYCLOHEXYLAMINO)-3-(6-METHYL-3,4-DIHYDRO-1H-CARBAZOL-9(2H)-YL)PROPAN-2-OL (3 entities in total)
• 機能のキーワード: antifungal drug, non-peptidic inhibitor, transferase
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• 細胞内の位置: Cytoplasm: P14743
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 324016.64

構造登録者

Wu, J.,Ding, J. (登録日: 2007-03-18, 公開日: 2007-06-12, 最終更新日: 2024-03-13)

主引用文献

Wu, J.,Tao, Y.,Zhang, M.,Howard, M.H.,Gutteridge, S.,Ding, J.
Crystal structures of Saccharomyces cerevisiae N-myristoyltransferase with bound myristoyl-CoA and inhibitors reveal the functional roles of the N-terminal region.
J.Biol.Chem., 282:22185-22194, 2007

PubMed Abstract: Protein N-myristoylation catalyzed by myristoyl-CoA:protein N-myristoyltransferase (NMT) plays an important role in a variety of critical cellular processes and thus is an attractive target for development of antifungal drugs. We report here three crystal structures of Saccharomyces cerevisiae NMT: in binary complex with myristoyl-CoA (MYA) alone and in two ternary complexes involving MYA and two different non-peptidic inhibitors. In all three structures, the majority of the N-terminal region, absent in all previously reported structures, forms a well defined motif that is located in the vicinity of the peptide substrate-binding site and is involved in the binding of MYA. The Ab loop, which might be involved in substrate recognition, adopts an open conformation, whereas a loop of the N-terminal region (residues 22-24) that covers the top of the substrate-binding site is in the position occupied by the Ab loop when in the closed conformation. Structural comparisons with other NMTs, together with mutagenesis data, suggest that the N-terminal region of NMT plays an important role in the binding of both MYA and peptide substrate, but not in subsequent steps of the catalytic mechanism. The two inhibitors occupy the peptide substrate-binding site and interact with the protein through primarily hydrophobic contacts. Analyses of the inhibitorenzyme interactions provide valuable information for further improvement of antifungal inhibitors targeting NMT.

PubMed: 17513302
DOI: 10.1074/jbc.M702696200

実験手法

X-RAY DIFFRACTION (3 Å)