Structural highlights
Function
[RS27A_BOVIN] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). Ribosomal protein S27a is a component of the 40S subunit of the ribosome.
Publication Abstract from PubMed
This work describes interaction of a family of [Pt(N(wedge)C)(PR3)Cl] complexes with imidazole (Im), possible application of this chemistry for regioselective labeling of proteins through imidazole rings of histidine residues and employment of the resulting phosphorescent products in bioimaging. It was found that the complexes containing aliphatic phosphines display reversible substitution of chloride ligand for imidazole function that required considerable excess of imidazole to obtain full conversion into the substituted [Pt(ppy)(PR3)(Im)] product, whereas the substitution in the complexes with aromatic phosphines readily proceeds in 1:1.5 mixture of reagents. Rapid, selective, and quantitative coordination of imidazole to the platinum complexes enabled regioselective labeling of ubiquitin. X-ray protein crystallography of the {[Pt(ppy)(PPh3)]/ubiquitin} conjugate revealed direct bonding of the platinum center to unique histidine-68 residue through the nitrogen atom of imidazole function, the coordination being also supported by noncovalent interaction of the ligands with the protein secondary structure. The variations of the cyclometalating N(wedge)C ligands gave a series of [Pt(N(wedge)C)(PPh3)Cl] complexes (N(wedge)C = 2-phenylpyridine, 2-(benzofuran-3-yl)pyridine, 2-(benzo[b]thiophen-3-yl)pyridine, methyl-2-phenylquinoline-4-carboxylate), which were used to investigate the impact of N(wedge)C-ligand onto photophysical properties of the imidazole complexes and conjugates with human serum albumin (HSA). The chloride ligand substitution for imidazole and formation of the conjugates results in ignition of the platinum chromophore luminescence with substantially higher quantum yield in the latter case. Variation of the metalating N(wedge)C-ligand made possible the shift of the emission to the red region of visible spectrum for both types of the products. Cell-viability tests revealed low cytotoxicity of all {[Pt(N(wedge)C)(PPh3)Cl]/HSA} conjugates, while PLIM experiments demonstrated their high potential for oxygen sensing.
Reactions of Cyclometalated Platinum(II) [Pt(N(wedge)C)(PR3)Cl] Complexes with Imidazole and Imidazole-Containing Biomolecules: Fine-Tuning of Reactivity and Photophysical Properties via Ligand Design.,Solomatina AI, Chelushkin PS, Abakumova TO, Zhemkov VA, Kim M, Bezprozvanny I, Gurzhiy VV, Melnikov AS, Anufrikov YA, Koshevoy IO, Su SH, Chou PT, Tunik SP Inorg Chem. 2018 Oct 30. doi: 10.1021/acs.inorgchem.8b02204. PMID:30376305[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Solomatina AI, Chelushkin PS, Abakumova TO, Zhemkov VA, Kim M, Bezprozvanny I, Gurzhiy VV, Melnikov AS, Anufrikov YA, Koshevoy IO, Su SH, Chou PT, Tunik SP. Reactions of Cyclometalated Platinum(II) [Pt(N(wedge)C)(PR3)Cl] Complexes with Imidazole and Imidazole-Containing Biomolecules: Fine-Tuning of Reactivity and Photophysical Properties via Ligand Design. Inorg Chem. 2018 Oct 30. doi: 10.1021/acs.inorgchem.8b02204. PMID:30376305 doi:http://dx.doi.org/10.1021/acs.inorgchem.8b02204
