Sirtuin4 (Sirt4) is one of the mammalian homologues of Silent information regulator 2 (Sir2), which promotes the longevity of yeast, C. elegans, fruit flies and mice. Sirt4 is localized in the mitochondria, where it contributes to preventing the development of cancers and ischemic heart disease through regulating energy metabolism. The ADP-ribosylation of glutamate dehydrogenase (GDH), which is catalyzed by Sirt4, downregulates the TCA cycle. However, this reaction mechanism is obscure, because the structure of Sirt4 is unknown. We here constructed structural models of Sirt4 by homology modeling and threading, and docked nicotinamide adenine dinucleotide+ (NAD+) to Sirt4. In addition, a partial GDH structure was docked to the Sirt4-NAD+ complex model. In the ternary complex model of Sirt4-NAD+-GDH, the acetylated lysine 171 of GDH is located close to NAD+. This suggests a possible mechanism underlying the ADP-ribosylation at cysteine 172, which may occur through a transient intermediate with ADP-ribosylation at the acetylated lysine 171. These results may be useful in designing drugs for the treatment of cancers and ischemic heart disease.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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