5H9D

Crystal structure of Heptaprenyl Diphosphate Synthase from Staphylococcus aureus

5H9D の概要

• エントリーDOI: 10.2210/pdb5h9d/pdb
• 分子名称: Farnesyl pyrophosphate synthetase, Heptaprenyl diphosphate synthase (HEPPP synthase) subunit 1 family protein, C-terminal peptide from Heptaprenyl diphosphate synthase (HEPPP synthase) subunit 1 family protein, ... (5 entities in total)
• 機能のキーワード: metal-binding, substrate binding, acidocalcisomal pyrophosphatase, transferase
• 由来する生物種: Staphylococcus aureus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 121338.39

構造登録者

Wei, H.L.,Liu, W.D.,Zheng, Y.Y.,Ko, T.P.,Chen, C.C.,Guo, R.T. (登録日: 2015-12-28, 公開日: 2016-12-28, 最終更新日: 2024-03-20)

主引用文献

Desai, J.,Liu, Y.L.,Wei, H.,Liu, W.,Ko, T.P.,Guo, R.T.,Oldfield, E.
Structure, Function, and Inhibition of Staphylococcus aureus Heptaprenyl Diphosphate Synthase
ChemMedChem, 11:1915-1923, 2016

PubMed Abstract: We report the first structure of heptaprenyl diphosphate synthase from Staphylococcus aureus (SaHepPPS), together with an investigation of its mechanism of action and inhibition. The protein is involved in the formation of menaquinone, a key electron transporter in many bacteria, including pathogens. SaHepPPS consists of a "catalytic " subunit (SaHepPPS-2) having two "DDXXD" motifs and a "regulatory" subunit (SaHepPPS-1) that lacks these motifs. High concentrations of the substrates, isopentenyl diphosphate and farnesyl diphosphate, inhibit the enzyme, which is also potently inhibited by bisphosphonates. The most active inhibitors (Ki ∼200 nm) were N-alkyl analogues of zoledronate containing ∼C6 alkyl side chains. They were modestly active against S. aureus cell growth, and growth inhibition was partially "rescued" by the addition of menaquinone-7. Because SaHepPPS is essential for S. aureus cell growth, its structure is of interest in the context of the development of menaquinone biosynthesis inhibitors as potential antibiotic leads.

PubMed: 27457559
DOI: 10.1002/cmdc.201600311

実験手法

X-RAY DIFFRACTION (2.68 Å)