9DQ7

Borrelia burgdorferi LDH with NADH, oxamate and FBS

9DQ7 の概要

• エントリーDOI: 10.2210/pdb9dq7/pdb
• 分子名称: L-lactate dehydrogenase, [[(2~{R},3~{S},4~{R},5~{R})-5-(5-aminocarbonyl-2~{H}-pyridin-1-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] [(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl hydrogen phosphate, OXAMIC ACID, ... (6 entities in total)
• 機能のキーワード: lactate dehydrogenase, fbs, oxamate, nadh, oxidoreductase
• 由来する生物種: Borreliella burgdorferi (Lyme disease spirochete)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 142213.92

構造登録者

Lynch, M.J. (登録日: 2024-09-23, 公開日: 2025-03-12, 最終更新日: 2025-09-24)

主引用文献

Sze, C.W.,Lynch, M.J.,Zhang, K.,Neau, D.B.,Ealick, S.E.,Crane, B.R.,Li, C.
Lactate dehydrogenase is the Achilles' heel of Lyme disease bacterium Borreliella burgdorferi.
Mbio, 16:e0372824-e0372824, 2025

PubMed Abstract: As a zoonotic pathogen, the Lyme disease bacterium has evolved unique metabolic pathways, some of which are specific and essential for its survival and thus present as ideal targets for developing new therapeutics. dispenses with the use of thiamin as a cofactor and relies on lactate dehydrogenase (BbLDH) to convert pyruvate to lactate for balancing NADH/NAD ratios. This report first demonstrates that BbLDH is a canonical LDH with some unique biochemical and structural features. A loss-of-function study then reveals that BbLDH is essential for survival and infectivity, highlighting its therapeutic potential. Drug screening identifies four previously unknown LDH inhibitors with minimal cytotoxicity, two of which inhibit growth. This study provides mechanistic insights into the function of BbLDH in the pathophysiology of and lays the groundwork for developing genus-specific metabolic inhibitors against and potentially other tick-borne pathogens as well.

PubMed: 40111021
DOI: 10.1128/mbio.03728-24

実験手法

X-RAY DIFFRACTION (2.11 Å)