6AS5

CRYSTAL STRUCTURE OF PROTEIN CitE FROM MYCOBACTERIUM TUBERCULOSIS IN COMPLEX WITH MAGNESIUM, ACETOACETATE AND COENZYME A

6AS5 の概要

• エントリーDOI: 10.2210/pdb6as5/pdb
• 関連するPDBエントリー: 6AQ4 6ARB
• 分子名称: Citrate lyase subunit beta-like protein, MAGNESIUM ION, COENZYME A, ... (7 entities in total)
• 機能のキーワード: protein cite, mycobacterium tuberculosis, acetoacetate, coenzyme a, tim-barrel, lyase
• 由来する生物種: Mycobacterium tuberculosis H37Rv
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 93009.98

構造登録者

Fedorov, A.A.,Fedorov, E.V.,Wang, H.,Bonanno, J.B.,Carvalho, L.,Almo, S.C. (登録日: 2017-08-23, 公開日: 2018-08-01, 最終更新日: 2023-10-25)

主引用文献

Wang, H.,Fedorov, A.A.,Fedorov, E.V.,Hunt, D.M.,Rodgers, A.,Douglas, H.L.,Garza-Garcia, A.,Bonanno, J.B.,Almo, S.C.,de Carvalho, L.P.S.
An essential bifunctional enzyme inMycobacterium tuberculosisfor itaconate dissimilation and leucine catabolism.
Proc.Natl.Acad.Sci.USA, 116:15907-15913, 2019

PubMed Abstract: (Mtb) is the etiological agent of tuberculosis. One-fourth of the global population is estimated to be infected with Mtb, accounting for ∼1.3 million deaths in 2017. As part of the immune response to Mtb infection, macrophages produce metabolites with the purpose of inhibiting or killing the bacterial cell. Itaconate is an abundant host metabolite thought to be both an antimicrobial agent and a modulator of the host inflammatory response. However, the exact mode of action of itaconate remains unclear. Here, we show that Mtb has an itaconate dissimilation pathway and that the last enzyme in this pathway, Rv2498c, also participates in l-leucine catabolism. Our results from phylogenetic analysis, in vitro enzymatic assays, X-ray crystallography, and in vivo Mtb experiments, identified Mtb Rv2498c as a bifunctional β-hydroxyacyl-CoA lyase and that deletion of the gene from the Mtb genome resulted in attenuation in a mouse infection model. Altogether, this report describes an itaconate resistance mechanism in Mtb and an l-leucine catabolic pathway that proceeds via an unprecedented ()-3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) stereospecific route in nature.

PubMed: 31320588
DOI: 10.1073/pnas.1906606116

実験手法

X-RAY DIFFRACTION (2.035 Å)