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Title | High-resolution structural-omics of human liver enzymes. |
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Journal, issue, pages | Cell Rep, Vol. 42, Issue 6, Page 112609, Year 2023 |
Publish date | Jun 27, 2023 |
![]() | Chih-Chia Su / Meinan Lyu / Zhemin Zhang / Masaru Miyagi / Wei Huang / Derek J Taylor / Edward W Yu / ![]() |
PubMed Abstract | We applied raw human liver microsome lysate to a holey carbon grid and used cryo-electron microscopy (cryo-EM) to define its composition. From this sample we identified and simultaneously determined ...We applied raw human liver microsome lysate to a holey carbon grid and used cryo-electron microscopy (cryo-EM) to define its composition. From this sample we identified and simultaneously determined high-resolution structural information for ten unique human liver enzymes involved in diverse cellular processes. Notably, we determined the structure of the endoplasmic bifunctional protein H6PD, where the N- and C-terminal domains independently possess glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase enzymatic activity, respectively. We also obtained the structure of heterodimeric human GANAB, an ER glycoprotein quality-control machinery that contains a catalytic α subunit and a noncatalytic β subunit. In addition, we observed a decameric peroxidase, PRDX4, which directly contacts a disulfide isomerase-related protein, ERp46. Structural data suggest that several glycosylations, bound endogenous compounds, and ions associate with these human liver enzymes. These results highlight the importance of cryo-EM in facilitating the elucidation of human organ proteomics at the atomic level. |
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Methods | EM (single particle) |
Resolution | 2.64 - 3.47 Å |
Structure data | EMDB-26915, PDB-7uzm: EMDB-28214, PDB-8ekw: EMDB-28217, PDB-8eky: EMDB-28232, PDB-8em2: EMDB-28262, PDB-8emr: EMDB-28263, PDB-8ems: EMDB-28264, PDB-8emt: EMDB-28271, PDB-8ene: EMDB-28377, PDB-8eoj: EMDB-28465, PDB-8eor: |
Chemicals | ![]() ChemComp-HOH: ![]() ChemComp-NAG: ![]() ChemComp-CA: ![]() ChemComp-PLP: ![]() ChemComp-FES: ![]() ChemComp-MTE: ![]() ChemComp-MOS: ![]() ChemComp-FAD: ![]() ChemComp-NAD: ![]() ChemComp-EEE: |
Source |
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![]() | OXIDOREDUCTASE / aldehyde dehydrogenase / human liver / Peroxiredoxin-4 / H6PD / HYDROLASE / glucosidase II / GANAB / glycosyl hydrolase 31 family / Glycogen Phosphorylase / PLP / Aldehyde oxidase / AOX1 / TRANSPORT PROTEIN / Microsomal triglyceride transfer protein / LIPID TRANSPORT / ISOMERASE / carboxylesterase |