GoKawiilThe cryo-EM maps and atomic coordinates for the eight UGCG structures reported in this study have been deposited in the Electron Microscopy Data Bank and PDB, respectively, under the following accession codes: apo UGCG, EMD-80823 and PDB 26QF; UGCG bound to UDP-glucose, EMD-80832 and PDB 26QS; UGCG bound to UDP, EMD-80833 and PDB 26QT; UGCG bound to UDP-glucose and PS, EMD-80829 and PDB 26QM; UGCG bound to UDP and C6-ceramide, EMD-80824 and PDB 26QG; UGCG bound to miglustat, EMD-80827 and PDB 26QJ; UGCG bound to ibiglustat, EMD-80826 and PDB 26QI; and UGCG bound to eliglustat, EMD-80825 and PDB 26QH. The reference structure of Chlorella virus hyaluronan synthase used for structural comparison is available from the PDB under accession code 7SP7. Structural homology searches were performed against the PDB and AlphaFold Database. For molecular dynamics simulations, simulation input files, including initial system coordinate, topology and force-field files, equilibration configuration files and run scripts, as well as final output coordinate files, are available at Zenodo (https://doi.org/10.5281/zenodo.20809831)45. For sequence data sources: the amino acid sequences of UGCG analysed in this study were obtained from the NCBI protein database. The specific accession numbers for the species used in the phylogenetic analysis are as follows: Prototheria: Ornithorhynchus anatinus (platypus, XP_028909707.1), Tachyglossus aculeatus (echidna, XP_038626167.1); Metatheria: Monodelphis domestica (opossum, XP_001365801.1), Notamacropus eugenii (tammar wallaby, XP_072454167.1), Phascolarctos cinereus (koala, XP_020828114.1), Vombatus ursinus (wombat, XP_027695337.1), Sarcophilus harrisii (Tasmanian devil, XP_003761468.2); Afrotheria: Loxodonta africana (African elephant, XP_003407853.1), Trichechus manatus (manatee, XP_004372220.1), Orycteropus afer (aardvark, XP_007934906.1), Echinops telfairi (tenrec, XP_012862260.1); Xenarthra: Dasypus novemcinctus (armadillo, XP_058158524.1); Laurasiatheria: Erinaceus europaeus (hedgehog, XP_007529571.1), Myotis lucifugus (bat, XP_023609045.1), Equus caballus (Horse, XP_001490953.3), Tursiops truncatus (dolphin/whale, XP_073662506.1), Canis lupus familiaris (dog, NP_001165706.1), Felis catus (cat, XP_011286799.1), Manis javanica (pangolin, XP_017515964.1); Euarchontoglires: Mus musculus (mouse, NP_035803.1), Oryctolagus cuniculus (rabbit, XP_069911685.1), Tupaia belangeri (tree shrew, ELW70583.1), Carlito syrichta (tarsier, XP_008064016.1), Macaca mulatta (monkey, NP_001244652.1) and Homo sapiens (human, NP_003349.1). Source data are provided with this paper.
Primate-specific regulation of the human glycosphingolipid gatekeeper UGCG
Why This Matters
This study provides detailed structural insights into the human glycosphingolipid gatekeeper UGCG, revealing primate-specific regulatory mechanisms. These findings could influence the development of targeted therapies for diseases involving glycosphingolipids and enhance our understanding of species-specific enzyme regulation in the tech-driven field of biomedical research. The deposited cryo-EM structures and molecular data serve as valuable resources for future drug design and functional studies.
Key Takeaways
- Provides high-resolution structures of UGCG in various bound states, aiding drug development.
- Highlights primate-specific regulation, emphasizing evolutionary differences in enzyme control.
- Offers extensive molecular data for computational modeling and further research.
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