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High-resolution structural-omics of human liver enzymes
Chih-Chia Su1, Meinan Lyu1, Zhemin Zhang1
1Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Cell Reports
|June 8, 2023
Summary
Cryo-electron microscopy revealed the atomic structures of ten human liver enzymes, including H6PD and GANAB. This technique advances understanding of human organ proteomics and enzyme function.
Area of Science:
- Biochemistry
- Structural Biology
- Proteomics
Background:
- Human liver enzymes are crucial for diverse cellular functions.
- Understanding their structure is key to elucidating biological pathways.
Purpose of the Study:
- To define the composition of human liver microsomes.
- To determine high-resolution structures of liver enzymes using cryo-electron microscopy (cryo-EM).
Main Methods:
- Applied raw human liver microsome lysate to a holey carbon grid.
- Utilized cryo-electron microscopy (cryo-EM) for structural determination.
Main Results:
- Identified and determined structures of ten unique human liver enzymes.
- Elucidated the structure of endoplasmic bifunctional protein H6PD and heterodimeric GANAB.
- Observed interactions between PRDX4 and ERp46, with associated glycosylations, compounds, and ions.
Conclusions:
- Cryo-EM is vital for atomic-level elucidation of human organ proteomics.
- Structural insights into liver enzymes advance understanding of cellular processes.
Keywords:
CP: MetabolismCP: Molecular biologyaldehyde oxidase 1carboxylesterase 1glucosidase IIglutamate dehydrogenase 1glycogen phosphorylasehexose-6-phosphate dehydrogenasemicrosomal triglyceride transfer protein complexperoxiredoxin 4 – endoplasmic reticulum protein 46 complexretinaldehyde dehydrogenase 1structural-omics
