7KL7

Helicobacter pylori Xanthine-Guanine-Hypoxanthine Phosphoribosyltransferase

7KL7 の概要

• エントリーDOI: 10.2210/pdb7kl7/pdb
• 分子名称: Phosphoribosyltransferase, SULFATE ION (3 entities in total)
• 機能のキーワード: helicobacter pylori xanthine-guanine-hypoxanthine phosphoribosyltransferase drug discovery nucleoside phosphates, transferase
• 由来する生物種: Helicobacter pylori
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37408.62

構造登録者

Guddat, L.W.,Keough, D.T. (登録日: 2020-10-29, 公開日: 2021-05-05, 最終更新日: 2024-03-06)

主引用文献

Keough, D.T.,Wun, S.J.,Baszczynski, O.,Eng, W.S.,Spacek, P.,Panjikar, S.,Naesens, L.,Pohl, R.,Rejman, D.,Hockova, D.,Ferrero, R.L.,Guddat, L.W.
Helicobacter pylori Xanthine-Guanine-Hypoxanthine Phosphoribosyltransferase-A Putative Target for Drug Discovery against Gastrointestinal Tract Infections.
J.Med.Chem., 64:5710-5729, 2021

PubMed Abstract: (Hp) is a human pathogen that lives in the gastric mucosa of approximately 50% of the world's population causing gastritis, peptic ulcers, and gastric cancer. An increase in resistance to current drugs has sparked the search for new Hp drug targets and therapeutics. One target is the disruption of nucleic acid production, which can be achieved by impeding the synthesis of 6-oxopurine nucleoside monophosphates, the precursors of DNA and RNA. These metabolites are synthesized by Hp xanthine-guanine-hypoxanthine phosphoribosyltransferase (XGHPRT). Here, nucleoside phosphonates have been evaluated, which inhibit the activity of this enzyme with values as low as 200 nM. The prodrugs of these compounds arrest the growth of Hp at a concentration of 50 μM in cell-based assays. The kinetic properties of HpXGHPRT have been determined together with its X-ray crystal structure in the absence and presence of 9-[(-3-phosphonopropyl)-aminomethyl-9-deazahypoxanthine, providing a basis for new antibiotic development.

PubMed: 33891818
DOI: 10.1021/acs.jmedchem.0c02184

実験手法

X-RAY DIFFRACTION (1.47 Å)