Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Primate-specific regulation of the human glycosphingolipid gatekeeper UGCG.
Journal, issue, pages	Nature, Year 2026
Publish date	Aug 26, 2026
Authors	Canrong Wu / Sanshan Jin / Jiuyin Xu / James Jiqi Wang / Xiaoqi Guo / Yunhai Li / Zhenyu Cao / Mengting Jiang / Qingning Yuan / Wen Hu / Changyao Li / Youwei Xu / Ming-Wei Wang / Yi Jiang / H Eric Xu /
PubMed Abstract	Glycosphingolipids are essential membrane components that organize lipid microdomains and orchestrate cellular signalling, differentiation and neuronal function. In humans, these functions arise from ...Glycosphingolipids are essential membrane components that organize lipid microdomains and orchestrate cellular signalling, differentiation and neuronal function. In humans, these functions arise from a repertoire of several hundred glycosphingolipid species generated through stepwise glycan elaboration. Entry into this network is controlled by a single committed reaction catalysed by UDP-glucose ceramide glucosyltransferase (UGCG), the gatekeeper that dictates the scale and composition of glycosphingolipid diversity. Despite its biological and therapeutic importance, its mechanism and regulation have remained unknown. Here we report cryogenic electron microscopy structures of full-length human UGCG in eight functional states at 2.9-3.4 Å resolution. UGCG adopts a previously unrecognized triple-pass transmembrane architecture that anchors a GT-A core at the membrane interface and creates a bipartite active site engaging soluble and membrane-embedded substrates. Contrary to canonical GT-A enzymes, UGCG uses a metal-independent catalytic mechanism driven by an arginine network. We identify a primate-specific steric element that tunes lipid affinity and catalytic turnover, modulating glycosphingolipid entry. Structures with clinically used inhibitors reveal how this architecture governs their potency and selectivity. Together, these findings define the structural and evolutionary logic by which one enzyme controls glycosphingolipid diversity and provide a framework for precision modulation of membrane lipid homeostasis in disease.
External links	Nature / PubMed:42649293
Methods	EM (single particle)
Resolution	2.88 - 3.43 Å
Structure data	80823 26qf EMDB-80823, PDB-26qf: Cryo-EM structure of human Ceramide glucosyltransferase UGCG Method: EM (single particle) / Resolution: 3.22 Å 80824 26qg EMDB-80824, PDB-26qg: Cryo-EM structure of human UGCG bound to UDP and C6-ceramide Method: EM (single particle) / Resolution: 3.2 Å 80825 26qh EMDB-80825, PDB-26qh: Cryo-EM structure of human UGCG bound to Eliglustat Method: EM (single particle) / Resolution: 3.23 Å 80826 26qi EMDB-80826, PDB-26qi: Cryo-EM structure of human UGCG bound to Ibiglustat Method: EM (single particle) / Resolution: 3.43 Å 80827 26qj EMDB-80827, PDB-26qj: Cryo-EM structure of human UGCG bound to Miglustat Method: EM (single particle) / Resolution: 3.34 Å 80829 26qm EMDB-80829, PDB-26qm: Cryo-EM structure of human UGCG bound to UDP-glucose and a phospholipid Method: EM (single particle) / Resolution: 3.07 Å 80832 26qs EMDB-80832, PDB-26qs: Cryo-EM structure of human UGCG bound to UDP-Glucose Method: EM (single particle) / Resolution: 2.88 Å 80833 26qt EMDB-80833, PDB-26qt: Cryo-EM structure of human UGCG bound to UDP Method: EM (single particle) / Resolution: 3.06 Å
Chemicals	ChemComp-6CM: N-((E,2S,3R)-1,3-DIHYDROXYOCTADEC-4-EN-2-YL)HEXANAMIDE ChemComp-UDP: URIDINE-5'-DIPHOSPHATE / UDPYM PDB-1e94: HslV-HslU from E.coli ChemComp-KYF: (1R,3S,4R)-1-azabicyclo[2.2.2]octan-3-yl {2-[2-(4-fluorophenyl)-1,3-thiazol-4-yl]propan-2-yl}carbamate ChemComp-CLR: CHOLESTEROL ChemComp-NBV: (2R,3R,4R,5S)-1-BUTYL-2-(HYDROXYMETHYL)PIPERIDINE-3,4,5-TRIOL ChemComp-UPG: URIDINE-5'-DIPHOSPHATE-GLUCOSE ChemComp-P5S*: O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine
Source	homo sapiens (human)
Keywords	TRANSFERASE / Ceramide glucosyltransferase / Ceramide glucosyltransferase;UGCG;GCS / Ceramide glucosyltransferase; UGCG; Eliglustat / Ceramide glucosyltransferase; UGCG;Ibiglustat / Ceramide glucosyltransferase; UGCG;Miglustat / Ceramide glucosyltransferase;UDP-Glucose