6OHO

Structure of human Phospholipase D2 catalytic domain

6OHO の概要

• エントリーDOI: 10.2210/pdb6oho/pdb
• 分子名称: Phospholipase D2, SULFATE ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: phosphodiesterase, hydrolase, hkd motif
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 148217.64

構造登録者

Metrick, C.M.,Chodaparambil, J.V. (登録日: 2019-04-06, 公開日: 2020-02-19, 最終更新日: 2024-10-09)

主引用文献

Metrick, C.M.,Peterson, E.A.,Santoro, J.C.,Enyedy, I.J.,Murugan, P.,Chen, T.,Michelsen, K.,Cullivan, M.,Spilker, K.A.,Kumar, P.R.,May-Dracka, T.L.,Chodaparambil, J.V.
Human PLD structures enable drug design and characterization of isoenzyme selectivity.
Nat.Chem.Biol., 16:391-399, 2020

PubMed Abstract: Phospholipase D enzymes (PLDs) are ubiquitous phosphodiesterases that produce phosphatidic acid (PA), a key second messenger and biosynthetic building block. Although an orthologous bacterial Streptomyces sp. strain PMF PLD structure was solved two decades ago, the molecular basis underlying the functions of the human PLD enzymes (hPLD) remained unclear based on this structure due to the low homology between these sequences. Here, we describe the first crystal structures of hPLD1 and hPLD2 catalytic domains and identify novel structural elements and functional differences between the prokaryotic and eukaryotic enzymes. Furthermore, structure-based mutation studies and structures of inhibitor-hPLD complexes allowed us to elucidate the binding modes of dual and isoform-selective inhibitors, highlight key determinants of isoenzyme selectivity and provide a basis for further structure-based drug discovery and functional characterization of this therapeutically important superfamily of enzymes.

PubMed: 32042197
DOI: 10.1038/s41589-019-0458-4

実験手法

X-RAY DIFFRACTION (2 Å)