6C85

Crystal structure of aspartate semialdehyde dehydrogenase from Blastomyces dermatitidis with p-benzoquinone

6C85 の概要

• エントリーDOI: 10.2210/pdb6c85/pdb
• 分子名称: Aspartate-semialdehyde dehydrogenase, 1,4-benzoquinone (3 entities in total)
• 機能のキーワード: rossman fold, oxidoreductase, antifungal inhibitor complex
• 由来する生物種: Blastomyces gilchristii (Blastomyces dermatitidis)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80522.14

構造登録者

Dahal, G.P.,Viola, R.E. (登録日: 2018-01-24, 公開日: 2019-01-30, 最終更新日: 2023-10-04)

主引用文献

Dahal, G.P.,Viola, R.E.
Structural insights into inhibitor binding to a fungal ortholog of aspartate semialdehyde dehydrogenase.
Biochem.Biophys.Res.Commun., 503:2848-2854, 2018

PubMed Abstract: The aspartate pathway, uniquely found in plants and microorganisms, offers novel potential targets for the development of new antimicrobial drugs. Aspartate semialdehyde dehydrogenase (ASADH) catalyzes production of a key intermediate at the first branch point in this pathway. Several fungal ASADH structures have been determined, but the prior crystallization conditions had precluded complex formation with enzyme inhibitors. The first inhibitor-bound and cofactor-bound structures of ASADH from the pathogenic fungi Blastomyces dermatitidis have now been determined, along with a structural and functional comparison to other ASADH family members. The structure of this new ASADH is similar to the other fungal orthologs, but with some critical differences in the orientation of some active site functional groups and in the subunit interface region. The presence of this bound inhibitor reveals the first details about inhibitor binding interactions, and the flexible orientation of its aromatic ring provides helpful insights into the design of potentially more potent and selective antifungal compounds.

PubMed: 30107909
DOI: 10.1016/j.bbrc.2018.08.053

実験手法

X-RAY DIFFRACTION (2.4 Å)