Dataset Information

High-resolution structural-omics of human liver enzymes.

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 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.

SUBMITTER: Su CC

PROVIDER: S-EPMC10592444 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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High-resolution structural-omics of human liver enzymes.

Su Chih-Chia CC Lyu Meinan M Zhang Zhemin Z Miyagi Masaru M Huang Wei W Taylor Derek J DJ Yu Edward W EW

Cell reports 20230607 6

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-phosph ...[more]

PMID: 37289586

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Project description:Objective: To investigate the correlation between the structure and function alterations of gut microbiota and biochemical indicators in males with hyperuricemia (HUA) and high levels of liver enzymes, in order to provide new evidences and therapeutic targets for the clinical diagnosis and treatment of HUA. Methods: A total of 69 patients with HUA (HUA group) and 118 healthy controls were enrolled in this study. Their age, height, waist circumference, weight, and pressure were measured. The clinical parameters such as fasting plasma glucose (FBG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum uric acid (SUA), serum creatinine (Scr), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), white blood cell (WBC), platelet (PLT), and absolute value of neutrophils (NEUT) were examined. We used whole-genome shotgun sequencing technology and HUMAnN2 MetaCyc pathway database to detect the composition and pathways of the gut microbiota. The main statistical methods were student's t test, chi-square tests, and Wilcoxon rank sum test. The correlations among bacterial diversity, microbial pathways, and biochemical indicators were evaluated by the R function "cor.test" with spearman method. Results: The gut bacterial diversity in HUA group reduced significantly and the community of the microbiota was of significant difference between the two groups. The pathways that can produce 5-aminoimidazole ribonucleotide (PWY-6122, PWY-6277, and PWY-6121), aromatic amino acids, and chorismate (COMPLETE-ARO-PWY, ARO-PWY, and PWY-6163) were enriched in the HUA group; while the pathways that can produce short-chain fatty acids (SCFAs, such as CENTFERM-PWY and PWY-6590) and the gut microbiotas that can produce SCFAs (Roseburia hominis, Odoribacter splanchnicus, Ruminococcus callidus, Lachnospiraceae bacterium 3_1_46FAA, Bacteroides uniformis, Butyricimonas synergistica) and equol (Adlercreutzia equolifaciens) were enriched in healthy controls. Conclusion: The structure and function of the gut microbiota in males with HUA and high levels of liver enzymes have altered apparently. In-depth study of related mechanisms may provide new ideas for the treatment of HUA.

Dataset Information

High-resolution structural-omics of human liver enzymes.

Publications

High-resolution structural-omics of human liver enzymes.

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