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Structure paper

TitleHigh-resolution structural-omics of human liver enzymes.
Journal, issue, pagesCell Rep, Vol. 42, Issue 6, Page 112609, Year 2023
Publish dateJun 27, 2023
AuthorsChih-Chia Su / Meinan Lyu / Zhemin Zhang / Masaru Miyagi / Wei Huang / Derek J Taylor / Edward W Yu /
PubMed AbstractWe 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.
External linksCell Rep / PubMed:37289586 / PubMed Central
MethodsEM (single particle)
Resolution2.64 - 3.47 Å
Structure data

26915

7uzm

EMDB-26915, PDB-7uzm:
Glutamate dehydrogenase 1 from human liver
Method: EM (single particle) / Resolution: 3.24 Å

28214

8ekw

EMDB-28214, PDB-8ekw:
Cryo-EM structure of human PRDX4
Method: EM (single particle) / Resolution: 2.83 Å

28217

8eky

EMDB-28217, PDB-8eky:
Cryo-EM structure of the human PRDX4-ErP46 complex
Method: EM (single particle) / Resolution: 3.47 Å

28232

8em2

EMDB-28232, PDB-8em2:
Cryo-EM structure of the human GDH/6PGL endoplasmic bifunctional protein
Method: EM (single particle) / Resolution: 3.02 Å

28262

8emr

EMDB-28262, PDB-8emr:
Cryo-EM structure of human liver glucosidase II
Method: EM (single particle) / Resolution: 2.92 Å

28263

8ems

EMDB-28263, PDB-8ems:
Cryo-EM structure of human liver glycogen phosphorylase
Method: EM (single particle) / Resolution: 2.65 Å

28264

8emt

EMDB-28264, PDB-8emt:
Cryo-EM analysis of the human aldehyde oxidase from liver
Method: EM (single particle) / Resolution: 2.92 Å

28271

8ene

EMDB-28271, PDB-8ene:
Aldehyde dehydrogenase 1 family member A1 from human liver
Method: EM (single particle) / Resolution: 2.64 Å

28377

8eoj

EMDB-28377, PDB-8eoj:
Microsomal triglyceride transfer protein
Method: EM (single particle) / Resolution: 3.07 Å

28465

8eor

EMDB-28465, PDB-8eor:
Liver carboxylesterase 1
Method: EM (single particle) / Resolution: 2.67 Å

Chemicals

ChemComp-HOH:
WATER

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-CA:
Unknown entry

ChemComp-PLP:
PYRIDOXAL-5'-PHOSPHATE

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER

ChemComp-MTE:
PHOSPHONIC ACIDMONO-(2-AMINO-5,6-DIMERCAPTO-4-OXO-3,7,8A,9,10,10A-HEXAHYDRO-4H-8-OXA-1,3,9,10-TETRAAZA-ANTHRACEN-7-YLMETHYL)ESTER

ChemComp-MOS:
DIOXOTHIOMOLYBDENUM(VI) ION

ChemComp-FAD:
FLAVIN-ADENINE DINUCLEOTIDE / FAD*YM

ChemComp-NAD:
NICOTINAMIDE-ADENINE-DINUCLEOTIDE / NAD*YM

ChemComp-EEE:
ETHYL ACETATE

Source
  • homo sapiens (human)
KeywordsOXIDOREDUCTASE / 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

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