Halogen bonds involved in binding of halogenated ligands by protein kinases.

Abstract:

:Analysis of 664 known structures of protein kinase complexes with halogenated ligands revealed 424 short contacts between a halogen atom and a potential protein X-bond acceptor, the topology and geometry of which were analyzed according to the type of a halogen atom (X = Cl, Br, I) and a putative protein X-bond acceptor. Among 236 identified halogen bonds, the most represented ones are directed to backbone carbonyls of the hinge region and may replace the pattern of ATP-like hydrogen bonds. Some halogen-π interactions with either aromatic residues or peptide bonds, that accompany the interaction with the hinge region, may possibly enhance ligand selectivity. Interestingly, many of these halogen-π interactions are bifurcated. Geometrical preferences identify iodine as the strongest X-bond donor, less so bromine, while virtually no such preferences were observed for chlorine; and a backbone carbonyl as the strongest X-bond acceptor. The presence of a halogen atom in a ligand additionally affects the properties of proximal hydrogen bonds, which according to geometrical parameters get strengthened, when a nitrogen of a halogenated ligand acts as the hydrogen bond donor.

journal_name

Acta Biochim Pol

journal_title

Acta biochimica Polonica

authors

Poznański J,Winiewska M,Czapinska H,Poznańska A,Shugar D

doi

10.18388/abp.2015_1106

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

203-14

issue

2

eissn

0001-527X

issn

1734-154X

pii

1645

journal_volume

63

pub_type

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