6HPS

Near-infrared dual bioluminescence imaging in vivo using infra-luciferin

6HPS の概要

• エントリーDOI: 10.2210/pdb6hps/pdb
• 分子名称: Luciferin 4-monooxygenase, [(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl ~{N}-[[2-[(~{E})-2-(6-oxidanyl-1,3-benzothiazol-2-yl)ethenyl]-1,3-thiazol-4-yl]carbonyl]sulfamate (2 entities in total)
• 機能のキーワード: near-infrared bioluminescence imaging, p. pyralis luciferase, anl superfamily, ligase, adenylating enzymes, luciferase, domain alternation, fluorescent protein
• 由来する生物種: Photinus pyralis (Common eastern firefly)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 121235.23

構造登録者

Parkinson, G.N.,Stowe, C.,Anderson, J.C. (登録日: 2018-09-21, 公開日: 2019-10-23, 最終更新日: 2024-01-24)

主引用文献

Stowe, C.L.,Burley, T.A.,Allan, H.,Vinci, M.,Kramer-Marek, G.,Ciobota, D.M.,Parkinson, G.N.,Southworth, T.L.,Agliardi, G.,Hotblack, A.,Lythgoe, M.F.,Branchini, B.R.,Kalber, T.L.,Anderson, J.C.,Pule, M.A.
Near-infrared dual bioluminescence imaging in mouse models of cancer using infraluciferin.
Elife, 8:-, 2019

PubMed Abstract: Bioluminescence imaging (BLI) is ubiquitous in scientific research for the sensitive tracking of biological processes in small animal models. However, due to the attenuation of visible light by tissue, and the limited set of near-infrared bioluminescent enzymes, BLI is largely restricted to monitoring single processes in vivo. Here we show, that by combining stabilised colour mutants of firefly luciferase (FLuc) with the luciferin (LH) analogue infraluciferin (iLH), near-infrared dual BLI can be achieved in vivo. The X-ray crystal structure of FLuc with a high-energy intermediate analogue, 5'-O-[N-(dehydroinfraluciferyl)sulfamoyl] adenosine (iDLSA) provides insight into the FLuc-iLH reaction leading to near-infrared light emission. The spectral characterisation and unmixing validation studies reported here established that iLH is superior to LH for the spectral unmixing of bioluminescent signals in vivo; which led to this novel near-infrared dual BLI system being applied to monitor both tumour burden and CAR T cell therapy within a systemically induced mouse tumour model.

PubMed: 31610848
DOI: 10.7554/eLife.45801

実験手法

X-RAY DIFFRACTION (3.1 Å)