A complex of atypical PKC and Par6 is a common regulator for cell polarity-related processes, which is an essential clue to evolutionary conserved cell polarity regulation. Here, we determined the crystal structure of the complex of PKCiota and Par6alpha PB1 domains to a resolution of 1.5 A. Both PB1 domains adopt a ubiquitin fold. PKCiota PB1 presents an OPR, PC, and AID (OPCA) motif, 28 amino...

A complex of atypical PKC and Par6 is a common regulator for cell-polarity related processes, which is an essential clue to evolutionary conserved cell-polarity regulation. Here, we determined the crystal structure of the complex of PKCι and Par6α PB1 domains to a resolution of 1.5 Å. Both PB1 domains adopt a ubiquitin fold. PKCι PB1 presents an OPCA motif, 28 amino acid residues with acidic an...

The packaging of eukaryotic DNA into chromatin is likely to be crucial for the maintenance of genomic integrity. Histone acetylation and deacetylation, which alter chromatin accessibility, have been implicated in DNA damage tolerance. Here we show that Schizosaccharomyces pombe Hst4, a homolog of histone deacetylase Sir2, participates in S-phase-specific DNA damage tolerance. Hst4 was essential...

Double-stranded DNA viruses package their genomes into procapsids via an ATP-driven nanomotor. This ingenious motor configuration has inspired the development of biomimetics in nanotechnology. Bacteriophage varphi29 DNA-packaging motor has been a popular tool in nanomedicine. To provide information for further motor modification, conjugation, labeling, and manufacturing, the connector protein g...

Mitotic cyclins are abruptly degraded at the end of mitosis by a cell-cycle-regulated ubiquitin-dependent proteolytic system. To understand how cyclin is recognized for ubiquitin conjugation, we have performed a mutagenic analysis of the destruction signal of mitotic cyclins. We demonstrate that an N-terminal cyclin B segment as short as 27 residues, containing the 9-amino-acid destruction box,...

A range of isoxazole-containing amino acids was synthesized that displaced acetyl-lysine-containing peptides from the BAZ2A, BRD4(1), and BRD9 bromodomains. Three of these amino acids were incorporated into a histone H4-mimicking peptide and their affinity for BRD4(1) was assessed. Affinities of the isoxazole-containing peptides are comparable to those of a hyperacetylated histone H4-mimicking ...

Saccharopine dehydrogenase (SDH) is the last enzyme in the AAA pathway of l-lysine biosynthesis. On the basis of crystal structures of SDH, the whole catalytic cycle of SDH has been studied by using density functional theory (DFT) method. Calculation results indicate that hydride transfer is the rate-limiting step with an energy barrier of 25.02kcal/mol, and the overall catalytic reaction is ca...

Silent information regulator 2 (Sir2) proteins (sirtuins) are nicotinamide adenine dinucleotide-dependent deacetylases that regulate important biological processes. Mammals have seven sirtuins, Sirt1 to Sirt7. Four of them (Sirt4 to Sirt7) have no detectable or very weak deacetylase activity. We found that Sirt5 is an efficient protein lysine desuccinylase and demalonylase in vitro. The prefere...

We report that a thiol leader peptidase, produced by replacing the critical serine at position 90 with a cysteine residue, is enzymatically active. In contrast to the wild-type leader peptidase, the thiol enzyme can be inactivated with N-ethylmaleimide, a cysteine-specific reagent. This strongly suggests that the serine 90 is involved in catalysis and is located at the active site. Of the three...

Homocysteine (hcy) is an intermediate metabolite in the metabolic pathway of cysteine and methionine. As a non-coded amino acid, hcy is not normally incorporated into protein. However, homocysteine can be recognized and activated by methionyl-tRNA synthetase (MetRs) to produce Hcy-thiolactone (HTL), which can react with the ε-amino group of a protein lysine residue. The N-hcy-linked protein car...