6K91

Pyridoxal Kinase from Leishmania donovani in complex with ADP and Pyridoxine

6K91 の概要

• エントリーDOI: 10.2210/pdb6k91/pdb
• 分子名称: Pyridoxal kinase, putative, ADENOSINE-5'-DIPHOSPHATE, 4,5-bis(hydroxymethyl)-2-methyl-pyridin-3-ol, ... (7 entities in total)
• 機能のキーワード: nucleotide binding, atp binding, kinase activity, metal binding, transferase
• 由来する生物種: Leishmania donovani (strain BPK282A1)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 72422.36

構造登録者

Are, S.,Gatreddi, S.,Qureshi, I.A. (登録日: 2019-06-13, 公開日: 2020-03-25, 最終更新日: 2024-03-27)

主引用文献

Are, S.,Gatreddi, S.,Jakkula, P.,Qureshi, I.A.
Structural attributes and substrate specificity of pyridoxal kinase from Leishmania donovani.
Int.J.Biol.Macromol., 152:812-827, 2020

PubMed Abstract: The enzyme pyridoxal kinase (PdxK) catalyzes the conversion of pyridoxal to pyridoxal-5'-phosphate (PLP) using ATP as the co-factor. The product pyridoxal-5'-phosphate plays a key role in several biological processes such as transamination, decarboxylation and deamination. In the present study, full-length ORF of PdxK from Leishmania donovani (LdPdxK) was cloned and then purified using affinity chromatography. LdPdxK exists as a homo-dimer in solution and shows more activity at near to physiological pH. Biochemical analysis of LdPdxK with pyridoxal, pyridoxamine, pyridoxine and ginkgotoxin revealed its affinity preference towards different substrates. The secondary structure analysis using circular dichroism spectroscopy showed LdPdxK to be predominantly α-helical in organization which tends to decline at lower and higher pH. Simultaneously, LdPdxK was crystallized and its three-dimensional structure in complex with ADP and different substrates were determined. Crystal structure of LdPdxK delineated that it has a central core of β-sheets surrounded by α-helices with a conserved GTGD ribokinase motif. The structures of LdPdxK disclosed no major structural changes between ADP and ADP- substrate bound structures. In addition, comparative structural analysis highlighted the key differences between the active site pockets of leishmanial and human PdxK, rendering LdPdxK an attractive candidate for the designing of novel and specific inhibitors.

PubMed: 32105687
DOI: 10.1016/j.ijbiomac.2020.02.257

実験手法

X-RAY DIFFRACTION (2 Å)