5XKP

Crystal structure of Msmeg3575 in complex with 5-azacytosine

5XKP の概要

• エントリーDOI: 10.2210/pdb5xkp/pdb
• 関連するPDBエントリー: 5XKO 5XKQ 5XKR
• 分子名称: CMP/dCMP deaminase, zinc-binding protein, 6-amino-1,3,5-triazin-2(1H)-one, ZINC ION, ... (6 entities in total)
• 機能のキーワード: hydrolase, deaminase, cda fold, 5-azacytosine
• 由来する生物種: Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 69666.18

構造登録者

Gaded, V.M.,Anand, R. (登録日: 2017-05-08, 公開日: 2017-08-09, 最終更新日: 2023-11-22)

主引用文献

Gaded, V.,Anand, R.
Selective Deamination of Mutagens by a Mycobacterial Enzyme
J. Am. Chem. Soc., 139:10762-10768, 2017

PubMed Abstract: Structure-based methods are powerful tools that are being exploited to unravel new functions with therapeutic advantage. Here, we report the discovery of a new class of deaminases, predominantly found in mycobacterial species that act on the commercially important s-triazine class of compounds. The enzyme Msd from Mycobacterium smegmatis was taken as a representative candidate from an evolutionarily conserved subgroup that possesses high density of Mycobacterium deaminases. Biochemical investigation reveals that Msd specifically acts on mutagenic nucleobases such as 5-azacytosine and isoguanine and does not accept natural bases as substrates. Determination of the X-ray structure of Msd to a resolution of 1.9 Å shows that Msd has fine-tuned its active site such that it is a hybrid of a cytosine as well as a guanine deaminase, thereby conferring Msd the ability to expand its repertoire to both purine and pyrimidine-like mutagens. Mapping of active site residues along with X-ray structures with a series of triazine analogues aids in deciphering the mechanism by which Msd proofreads the base milieu for mutagens. The genome location of the enzyme reveals that Msd is part of a conserved cluster that confers the organism with innate resistance toward select xenobiotics by triggering their efflux.

PubMed: 28708393
DOI: 10.1021/jacs.7b04967

実験手法

X-RAY DIFFRACTION (3 Å)