6HPS
Near-infrared dual bioluminescence imaging in vivo using infra-luciferin
Summary for 6HPS
Entry DOI | 10.2210/pdb6hps/pdb |
Descriptor | 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) |
Functional Keywords | near-infrared bioluminescence imaging, p. pyralis luciferase, anl superfamily, ligase, adenylating enzymes, luciferase, domain alternation, fluorescent protein |
Biological source | Photinus pyralis (Common eastern firefly) |
Total number of polymer chains | 2 |
Total formula weight | 121235.23 |
Authors | Parkinson, G.N.,Stowe, C.,Anderson, J.C. (deposition date: 2018-09-21, release date: 2019-10-23, Last modification date: 2024-01-24) |
Primary citation | 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 Cited by 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: 31610848DOI: 10.7554/eLife.45801 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (3.1 Å) |
Structure validation
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