7BRS

E.coli beta-galactosidase (E537Q) in complex with fluorescent probe KSA02

Summary for 7BRS

• Entry DOI: 10.2210/pdb7brs/pdb
• Descriptor: Beta-galactosidase, 8-[2-[(E)-2-[4-[(2S,3R,4S,5R,6R)-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxyphenyl]ethenyl]-3,3-dimethyl-indol-1-ium-1-yl]octanoic acid, MAGNESIUM ION, ... (7 entities in total)
• Functional Keywords: beta_galactosidase, fluorescent probe, hydrolase
• Biological source: Escherichia coli K-12
• Total number of polymer chains: 4
• Total formula weight: 473070.48

Authors

Chen, X.,Hu, Y.L.,Gao, Y.,Yuan, R.,Guo, Y. (deposition date: 2020-03-30, release date: 2021-03-03, Last modification date: 2023-11-29)

Primary citation

Gao, Y.,Hu, Y.,Liu, Q.,Li, X.,Li, X.,Kim, C.Y.,James, T.D.,Li, J.,Chen, X.,Guo, Y.
Two-Dimensional Design Strategy to Construct Smart Fluorescent Probes for the Precise Tracking of Senescence.
Angew.Chem.Int.Ed.Engl., 60:10756-10765, 2021

PubMed Abstract: The tracking of cellular senescence usually depends on the detection of senescence-associated β-galactosidase (SA-β-gal). Previous probes for SA-β-gal with this purpose only cover a single dimension: the accumulation of this enzyme in lysosomes. However, this is insufficient to determine the destiny of senescence because endogenous β-gal enriched in lysosomes is not only related to senescence, but also to some other physiological processes. To address this issue, we introduce our fluorescent probes including a second dimension: lysosomal pH, since de-acidification is a unique feature of the lysosomes in senescent cells. With this novel design, our probes achieved excellent discrimination of SA-β-gal from cancer-associated β-gal, which enables them to track cellular senescence as well as tissue aging more precisely. Our crystal structures of a model enzyme E. coli β-gal mutant (E537Q) complexed with each probe further revealed the structural basis for probe recognition.

PubMed: 33624914
DOI: 10.1002/anie.202101278

Experimental method

X-RAY DIFFRACTION (2.67 Å)