6BON

Crystal structure of 2-methylcitrate synthase from Aspergillus fumigatus with oxaloacetate and coenzyme-A.

6BON の概要

• エントリーDOI: 10.2210/pdb6bon/pdb
• 分子名称: 2-methylcitrate synthase, mitochondrial, OXALOACETATE ION, COENZYME A, ... (4 entities in total)
• 機能のキーワード: mcsa, 2-methylcitrate synthase, citrate synthase, transferase
• 由来する生物種: Neosartorya fumigata (strain CEA10 / CBS 144.89 / FGSC A1163) (Aspergillus fumigatus)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 98275.58

構造登録者

Schlachter, C.,Chruszcz, M. (登録日: 2017-11-20, 公開日: 2018-11-28, 最終更新日: 2023-10-04)

主引用文献

Schlachter, C.R.,Klapper, V.,Radford, T.,Chruszcz, M.
Comparative studies of Aspergillus fumigatus 2-methylcitrate synthase and human citrate synthase.
Biol.Chem., 400:1567-1581, 2019

PubMed Abstract: Aspergillus fumigatus is a ubiquitous fungus that is not only a problem in agriculture, but also in healthcare. Aspergillus fumigatus drug resistance is becoming more prominent which is mainly attributed to the widespread use of fungicides in agriculture. The fungi-specific 2-methylcitrate cycle is responsible for detoxifying propionyl-CoA, a toxic metabolite produced as the fungus breaks down proteins and amino acids. The enzyme responsible for this detoxification is 2-methylcitrate synthase (mcsA) and is a potential candidate for the design of new anti-fungals. However, mcsA is very similar in structure to human citrate synthase (hCS) and catalyzes the same reaction. Therefore, both enzymes were studied in parallel to provide foundations for design of mcsA-specific inhibitors. The first crystal structures of citrate synthase from humans and 2-methylcitrate synthase from A. fumigatus are reported. The determined structures capture various conformational states of the enzymes and several inhibitors were identified and characterized. Despite a significant homology, mcsA and hCS display pronounced differences in substrate specificity and cooperativity. Considering that the active sites of the enzymes are almost identical, the differences in reactions catalyzed by enzymes are caused by residues that are in the vicinity of the active site and influence conformational changes of the enzymes.

PubMed: 31141475
DOI: 10.1515/hsz-2019-0106

実験手法

X-RAY DIFFRACTION (2.35 Å)