5K9N

Structural and Mechanistic Analysis of Drosophila melanogaster Polyamine N acetyltransferase, an enzyme that Catalyzes the Formation of N acetylagmatine

5K9N の概要

• エントリーDOI: 10.2210/pdb5k9n/pdb
• 分子名称: Polyamine N acetyltransferase (2 entities in total)
• 機能のキーワード: polyamine n acetyltransferase, agmatine, n acetylagmatine, drosophila melanogaster, enzyme mechanism, acetyl-coa, and protein crystallography, transferase
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47598.22

構造登録者

Dempsey, D.R.,Nichols, D.A.,Battistini, M.R.,Pemberton, O.,Ospina, S.R.,Zhang, X.,Carpenter, A.-M.,Chen, Y.,Merkler, D.J. (登録日: 2016-06-01, 公開日: 2017-06-07, 最終更新日: 2024-02-28)

主引用文献

Dempsey, D.R.,Nichols, D.A.,Battistini, M.R.,Pemberton, O.,Ospina, S.R.,Zhang, X.,Carpenter, A.M.,O'Flynn, B.G.,Leahy, J.W.,Kanwar, A.,Lewandowski, E.M.,Chen, Y.,Merkler, D.J.
Structural and Mechanistic Analysis of Drosophila melanogaster Agmatine N-Acetyltransferase, an Enzyme that Catalyzes the Formation of N-Acetylagmatine.
Sci Rep, 7:13432-13432, 2017

PubMed Abstract: Agmatine N-acetyltransferase (AgmNAT) catalyzes the formation of N-acetylagmatine from acetyl-CoA and agmatine. Herein, we provide evidence that Drosophila melanogaster AgmNAT (CG15766) catalyzes the formation of N-acetylagmatine using an ordered sequential mechanism; acetyl-CoA binds prior to agmatine to generate an AgmNAT•acetyl-CoA•agmatine ternary complex prior to catalysis. Additionally, we solved a crystal structure for the apo form of AgmNAT with an atomic resolution of 2.3 Å, which points towards specific amino acids that may function in catalysis or active site formation. Using the crystal structure, primary sequence alignment, pH-activity profiles, and site-directed mutagenesis, we evaluated a series of active site amino acids in order to assign their functional roles in AgmNAT. More specifically, pH-activity profiles identified at least one catalytically important, ionizable group with an apparent pK of ~7.5, which corresponds to the general base in catalysis, Glu-34. Moreover, these data led to a proposed chemical mechanism, which is consistent with the structure and our biochemical analysis of AgmNAT.

PubMed: 29044148
DOI: 10.1038/s41598-017-13669-6

実験手法

X-RAY DIFFRACTION (2.3 Å)