8A21

Crystal structure of Phosphoserine phosphatase SerB from Mycobacterium avium in complex with phenylimidazole

8A21 の概要

• エントリーDOI: 10.2210/pdb8a21/pdb
• 分子名称: Phosphoserine phosphatase, MAGNESIUM ION, 4-PHENYL-1H-IMIDAZOLE, ... (6 entities in total)
• 機能のキーワード: phosphoserine phosphatase, avium, pim, phenylimidazole, hydrolase
• 由来する生物種: Mycobacterium avium 104
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44292.29

構造登録者

Haufroid, M.,Wouters, J. (登録日: 2022-06-02, 公開日: 2022-11-23, 最終更新日: 2024-01-31)

主引用文献

Haufroid, M.,Volkov, A.N.,Wouters, J.
Targeting the phosphoserine phosphatase MtSerB2 for tuberculosis drug discovery, an hybrid knowledge based /fragment based approach.
Eur.J.Med.Chem., 245:114935-114935, 2022

PubMed Abstract: Tuberculosis is currently still one of the leading causes of death from a treatable pathogen. The proportion of cases of resistance to common antibiotics is frequently increasing and the development of new drugs with new therapeutic targets is becoming necessary. The Mycobacterium tuberculosis phosphoserine phosphatase MtSerB2 is an interesting enzyme to target in drug design because of its ability to allow immune evasion of the bacteria. Research has already been carried out on this protein both from a mechanistic point of view and from the point of view of its inhibition by trisubstituted harmine derivatives. Based on this work, a new approach based on virtual screening is presented in the selection of fragment-sized harmine-derived compounds as well as chelators to target the catalytic magnesium of MtSerB2. The selection of a minimum list of fragments is explained as well as the screening cascade (DSF, Ligand-based NMR, High concentration enzymatic assay) to characterise their affinity for MtSerB2. Crystallogenesis assays have provided structural information on some promising fragments and the development of a pharmacophore model with the structural elements necessary for the development of more complex inhibitors. Ultimately, this work on fragment growth would allow the development of antimycobacterial molecules inhibiting MtSerB2 as well as the growth of the pathogen.

PubMed: 36403421
DOI: 10.1016/j.ejmech.2022.114935

実験手法

X-RAY DIFFRACTION (2.18 Å)