3TFY

Naa50p amino-terminal acetyltransferase bound to substrate peptide fragment and CoA

3TFY の概要

• エントリーDOI: 10.2210/pdb3tfy/pdb
• 関連するPDBエントリー: 2OB0 2PSW
• 分子名称: N-alpha-acetyltransferase 50, NatE catalytic subunit, hnRNP F, COENZYME A, ... (4 entities in total)
• 機能のキーワード: transferase, gnat family, n(alpha)-acetyltransferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q9GZZ1
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 63765.35

構造登録者

Liszczak, G.P.,Marmorstein, R. (登録日: 2011-08-16, 公開日: 2011-09-07, 最終更新日: 2023-09-13)

主引用文献

Liszczak, G.,Arnesen, T.,Marmorstein, R.
Structure of a Ternary Naa50p (NAT5/SAN) N-terminal Acetyltransferase Complex Reveals the Molecular Basis for Substrate-specific Acetylation.
J.Biol.Chem., 286:37002-37010, 2011

PubMed Abstract: The co-translational modification of N-terminal acetylation is ubiquitous among eukaryotes and has been reported to have a wide range of biological effects. The human N-terminal acetyltransferase (NAT) Naa50p (NAT5/SAN) acetylates the α-amino group of proteins containing an N-terminal methionine residue and is essential for proper sister chromatid cohesion and chromosome condensation. The elevated activity of NATs has also been correlated with cancer, making these enzymes attractive therapeutic targets. We report the x-ray crystal structure of Naa50p bound to a native substrate peptide fragment and CoA. We found that the peptide backbone of the substrate is anchored to the protein through a series of backbone hydrogen bonds with the first methionine residue specified through multiple van der Waals contacts, together creating an α-amino methionine-specific pocket. We also employed structure-based mutagenesis; the results support the importance of the α-amino methionine-specific pocket of Naa50p and are consistent with the proposal that conserved histidine and tyrosine residues play important catalytic roles. Superposition of the ternary Naa50p complex with the peptide-bound Gcn5 histone acetyltransferase revealed that the two enzymes share a Gcn5-related N-acetyltransferase fold but differ in their respective substrate-binding grooves such that Naa50p can accommodate only an α-amino substrate and not a side chain lysine substrate that is acetylated by lysine acetyltransferase enzymes such as Gcn5. The structure of the ternary Naa50p complex also provides the first molecular scaffold for the design of NAT-specific small molecule inhibitors with possible therapeutic applications.

PubMed: 21900231
DOI: 10.1074/jbc.M111.282863

実験手法

X-RAY DIFFRACTION (2.75 Å)