6KUZ
E.coli beta-galactosidase (E537Q) in complex with fluorescent probe KSL01
Summary for 6KUZ
| Entry DOI | 10.2210/pdb6kuz/pdb |
| Descriptor | Beta-galactosidase, 3-(1,3-benzothiazol-2-yl)-2-[[4-[(2~{S},3~{R},4~{S},5~{R},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxyphenyl]methoxy]-5-methyl-benzaldehyde, SODIUM 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 | 471853.33 |
| Authors | |
| Primary citation | Li, X.,Qiu, W.,Li, J.,Chen, X.,Hu, Y.,Gao, Y.,Shi, D.,Li, X.,Lin, H.,Hu, Z.,Dong, G.,Sheng, C.,Jiang, B.,Xia, C.,Kim, C.Y.,Guo, Y.,Li, J. First-generation species-selective chemical probes for fluorescence imaging of human senescence-associated beta-galactosidase. Chem Sci, 11:7292-7301, 2020 Cited by PubMed Abstract: Human senescence-associated β-galactosidase (SA-β-gal), the most widely used biomarker of aging, is a valuable tool for assessing the extent of cell 'healthy aging' and potentially predicting the health life span of an individual. Human SA-β-gal is an endogenous lysosomal enzyme expressed from , the catalytic domain of which is very different from that of β-gal, a bacterial enzyme encoded by . However, existing chemical probes for this marker still lack the ability to distinguish human SA-β-gal from β-gal of other species, such as bacterial β-gal, which can yield false positive signals. Here, we show a molecular design strategy to construct fluorescent probes with the above ability with the aid of structure-based steric hindrance adjustment catering to different enzyme pockets. The resulting probes normally work as traditional SA-β-gal probes, but they are unique in their powerful ability to distinguish human SA-β-gal from β-gal, thus achieving species-selective visualization of human SA-β-gal for the first time. NIR-emitting fluorescent probe as their representative further displays excellent species-selective recognition performance in biological systems, which has been herein verified by testing in senescent cells, in -transfected cells and in -β-gal-contaminated tissue sections of mice. Because of our probes, it was also discovered that SA-β-gal content in mice increased gradually with age and SA-β-gal accumulated most in the kidneys among the main organs of naturally aging mice, suggesting that the kidneys are the organs with the most severe aging during natural aging. PubMed: 34123013DOI: 10.1039/d0sc01234c PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.83 Å) |
Structure validation
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