4S1H
Pyridoxal kinase of Entamoeba histolytica with ADP
4S1H の概要
エントリーDOI | 10.2210/pdb4s1h/pdb |
関連するPDBエントリー | 4S1I |
分子名称 | Pyridoxal kinase, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total) |
機能のキーワード | pyridoxal 5'-phosphate, transferase |
由来する生物種 | Entamoeba histolytica |
タンパク質・核酸の鎖数 | 2 |
化学式量合計 | 65143.54 |
構造登録者 | Tarique, K.F.,Devi, S.,Abdul Rehman, S.A.,Gourinath, S. (登録日: 2015-01-13, 公開日: 2015-01-28, 最終更新日: 2024-04-03) |
主引用文献 | Tarique, K.F.,Devi, S.,Tomar, P.,Ali, M.F.,Rehman, S.A.A.,Gourinath, S. Characterization and functional insights into the Entamoeba histolytica pyridoxal kinase, an enzyme essential for its survival. J.Struct.Biol., 212:107645-107645, 2020 Cited by PubMed Abstract: Pyridoxal 5'-phosphate (PLP) is the active form of vitamin B and a cofactor for more than 140 enzymes. This coenzyme plays a pivotal role in catalysis of various enzymatic reactions that are critical for the survival of organisms. Entamoeba histolytica depends on the uptake of pyridoxal (PL), a B vitamer from the external environment which is then phosphorylated by pyridoxal kinase (EhPLK) to form PLP via the salvage pathway. E. histolytica cannot synthesise vitamin Bde-novo, and also lacks pyridoxine 5'-phosphate oxidase, a salvage pathway enzyme required to produce PLP from pyridoxine phosphate (PNP) and pyridoxamine phosphate (PMP). Analysing the importance of PLK in E. histolytica, we have determined the high-resolution crystal structures of the dimeric pyridoxal kinase in apo, ADP-bound, and PLP-bound states. These structures provided a snapshot of the transition state and help in understanding the reaction mechanism in greater detail. The EhPLK structure significantly differed from the human homologue at its PLP binding site, and the phylogenetic study also revealed its divergence from human PLK. Further, gene regulation of EhPLK using sense and antisense RNA showed that any change in optimal level is harmful to the pathogen. Biochemical and in vivo studies unveiled EhPLK to be essential for this pathogen, while the molecular differences with human PLK structure can be exploited for the structure-guided design of EhPLK inhibitors. PubMed: 33045383DOI: 10.1016/j.jsb.2020.107645 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (1.6 Å) |
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