Packing of aromatic rings against tryptophan residues in proteins

The geometry of the interaction of the aromatic side chains of phenylalanine (Phe), tyrosine (Tyr), tryptophan (Trp) and histidine (His) with the indole ring of Trp has been analyzed using the structures in the Protein Data Bank in order to understand the dependence of the packing behaviour on the size and chemical nature of the aromatic rings. The Phe ring prefers to interact either perpendicularly, with its edge pointing towards the Trp face, or in an offset-stacked arrangement. The edge-to-face motif is typical of a Trp–Trp pair. While parallel stacking is the dominant feature of Trp–His interaction, Tyr packs in a more uniform manner around Trp with a higher than expected occurrence at the edge and a few cases of possible OH–π interaction.

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Crystallography and chemistry should always go together: a cautionary tale of protein complexes with cisplatin and carboplatin

Acta Crystallographica Section D Biological Crystallography ◽

10.1107/s139900471500629x ◽

2015 ◽

Vol 71 (9) ◽

pp. 1965-1979 ◽

Cited By ~ 35

Author(s):

Ivan Shabalin ◽

Zbigniew Dauter ◽

Mariusz Jaskolski ◽

Wladek Minor ◽

Alexander Wlodawer

Keyword(s):

Side Effects ◽

Data Collection ◽

Anticancer Activity ◽

Crystal Structures ◽

Protein Data Bank ◽

Diffraction Data ◽

Chemical Nature ◽

Protein Complexes ◽

Data Bank ◽

Cautionary Tale

The anticancer activity of platinum-containing drugs such as cisplatin and carboplatin is considered to primarily arise from their interactions with nucleic acids; nevertheless, these drugs, or the products of their hydrolysis, also bind to proteins, potentially leading to the known side effects of the treatments. Here, over 40 crystal structures deposited in the Protein Data Bank (PDB) of cisplatin and carboplatin complexes of several proteins were analysed. Significant problems of either a crystallographic or a chemical nature were found in most of the presented atomic models and they could be traced to less or more serious deficiencies in the data-collection and refinement procedures. The re-evaluation of these data and models was possible thanks to their mandatory or voluntary deposition in publicly available databases, emphasizing the point that the availability of such data is critical for making structural science reproducible. Based on this analysis of a selected group of macromolecular structures, the importance of deposition of raw diffraction data is stressed and a procedure for depositing, tracking and using re-refined crystallographic models is suggested.

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An interesting possibility of forming special hole stepping stones with high-stacking aromatic rings in proteins: three-π five-electron and four-π seven-electron resonance bindings

RSC Advances ◽

10.1039/d1ra05341h ◽

2021 ◽

Vol 11 (43) ◽

pp. 26672-26682

Author(s):

Xin Li ◽

Weichao Sun ◽

Xin Qin ◽

Yuxin Xie ◽

Nian Liu ◽

...

Keyword(s):

Close Approach ◽

Side Chains ◽

Biological Processes ◽

Aromatic Rings ◽

Stepping Stones ◽

Long Distance ◽

Hole Transfer ◽

Electron Resonance ◽

Interesting Possibility ◽

Aromatic Side Chains

The three-π five-electron relay forming by three close approach aromatic side chains may promote hole transfer in proteins, supporting hole translocation across a long distance during sophisticated biological processes.

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