6RQE

CYP121 in complex with 3-acetylene dicyclotyrosine

6RQE の概要

• エントリーDOI: 10.2210/pdb6rqe/pdb
• 分子名称: Mycocyclosin synthase, SULFATE ION, 3-acetylene dicyclotyrosine, ... (5 entities in total)
• 機能のキーワード: cyp121, p450, dicyclotyrosine derivatives, heme, oxidoreductase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44656.97

構造登録者

Poddar, H.,Levy, C. (登録日: 2019-05-15, 公開日: 2020-04-22, 最終更新日: 2024-01-24)

主引用文献

Rajput, S.,McLean, K.J.,Poddar, H.,Selvam, I.R.,Nagalingam, G.,Triccas, J.A.,Levy, C.W.,Munro, A.W.,Hutton, C.A.
Structure-Activity Relationships ofcyclo(l-Tyrosyl-l-tyrosine) Derivatives Binding toMycobacterium tuberculosisCYP121: Iodinated Analogues Promote Shift to High-Spin Adduct.
J.Med.Chem., 62:9792-9805, 2019

PubMed Abstract: A series of analogues of (l-tyrosyl-l-tyrosine), the substrate of the enzyme CYP121, have been synthesized and analyzed by UV-vis and electron paramagnetic resonance spectroscopy and by X-ray crystallography. The introduction of iodine substituents onto (l-tyrosyl-l-tyrosine) results in sub-μM binding affinity for the CYP121 enzyme and a complete shift to the high-spin state of the heme Fe. The introduction of halogens that are able to interact with heme groups is thus a feasible approach to the development of next-generation, tight binding inhibitors of the CYP121 enzyme, in the search for novel antitubercular compounds.

PubMed: 31618032
DOI: 10.1021/acs.jmedchem.9b01199

実験手法

X-RAY DIFFRACTION (1.37 Å)