5X62

Crystal structure of a carnosine N-methyltransferase bound by AdoHcy

5X62 の概要

• エントリーDOI: 10.2210/pdb5x62/pdb
• 分子名称: Carnosine N-methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: methyltransferase, sam, rossmann fold, transferase
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 93044.41

構造登録者

Xie, W.,Liu, X. (登録日: 2017-02-20, 公開日: 2017-07-26, 最終更新日: 2024-11-06)

主引用文献

Liu, X.,Wu, J.,Sun, Y.,Xie, W.
Substrate Recognition Mechanism of the Putative Yeast Carnosine N-methyltransferase
ACS Chem. Biol., 12:2164-2171, 2017

PubMed Abstract: Anserine (β-alanyl-N(P)-methyl-l-histidine) is a natural metabolite present in skeletal muscle and the central nervous system of vertebrates and plays important physiological roles in living organisms. The production of anserine is catalyzed by carnosine N-methyltransferases, which transfer a methyl group to carnosine (β-alanyl-l-histidine). However, the structural basis of the substrate recognition for the enzymes is unknown. We present the crystal structure of the putative carnosine N-methyltransferase from yeast named YNL092W in complex with SAH, solved by the single-wavelength anomalous dispersion (SAD) method. The protein contains a typical Rossmann domain and a characteristic N-terminal helical domain. At the cofactor-binding site, SAH forms an extensive interaction network with the enzyme. The individual contribution of each residue to ligand affinity and enzyme activity was assessed by ITC and methyltransferase assays after mutagenesis of the key residues. Additionally, docking studies and activity assays were conducted in order to identify the binding site for carnosine, and a plausible complex model was proposed. Furthermore, we discovered that two disulfide bridges might be functionally important to the enzyme. By comparison to structure- and sequence-similar methyltransferases, we deduce that the enzyme most likely acts on a protein substrate. Our structural analyses shed light on the catalytic mechanism and substrate recognition by YNL092W.

PubMed: 28654751
DOI: 10.1021/acschembio.7b00328

実験手法

X-RAY DIFFRACTION (2.204 Å)