Guanidinium–amino acid hydrogen-bonding interactions in protein crystal structures: implications for guanidinium-induced protein denaturation

Authors

Indu Negi, Computational Biochemistry Laboratory, Department of Chemistry and Centre for Advanced Studies in Chemistry, Panjab University, Chandigarh
Raman Jangra, omputational Biochemistry Laboratory, Department of Chemistry and Centre for Advanced Studies in Chemistry, Panjab University, Chandigarh
Amit Gharu, Computational Biochemistry Laboratory, Department of Chemistry and Centre for Advanced Studies in Chemistry, Panjab University, Chandigarh
John F. Trant, Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Ave. Windsor ONFollow
Purshotam Sharma, Computational Biochemistry Laboratory, Department of Chemistry and Centre for Advanced Studies in Chemistry, Panjab University, ChandigarhFollow

Author ORCID Identifier

https://orcid.org/0000-0001-7813-1973 : Raman Jangra

https://orcid.org/0000-0002-4780-4968 : John F. Trant

Document Type

Article

Publication Date

12-8-2022

Publication Title

Physical Chemistry Chemical Physics

Volume

2023

Issue

25

First Page

857

Last Page

869

Abstract

In the present work, 86 available high resolution X-ray structures of proteins that contain one or more guanidinium ions (Gdm+) are analyzed for the distribution and nature of noncovalent interactions between Gdm+ and amino-acid residues. A total of 1044 hydrogen-bonding interactions were identified, of which 1039 are N–H⋯O, and five are N–H⋯N. Acidic amino acids are more likely to interact with Gdm+ (46% of interactions, 26% Asp and 20% Glu), followed by Pro (19% of interactions). DFT calculations on the identified Gdm+–amino acid hydrogen-bonded pairs reveal that although Gdm+ interacts primarily with the backbone amides of nonpolar amino acids, Gdm+ does interact with the sidechains of polar and acidic amino acids. We classified the optimized Gdm+–amino acid pairs into parallel [p], bifurcated [b], single hydrogen bonded [s] and triple hydrogen bonded [t] types. The [p] and [t] type pairs possess higher average interaction strength that is stronger than that of [b] and [s] type pairs. Negatively charged aspartate and glutamate residues interact with Gdm+ ion exceptionally tightly (−76 kcal mol−1) in [p] type complexes. This work provides statistical and energetics insights to better describe the observed destabilization or denaturation process of proteins by guanidinium salts.

ISSN

1463-9076

Recommended Citation

Negi, Indu; Jangra, Raman; Gharu, Amit; Trant, John F.; and Sharma, Purshotam. (2022). Guanidinium–amino acid hydrogen-bonding interactions in protein crystal structures: implications for guanidinium-induced protein denaturation. Physical Chemistry Chemical Physics, 2023 (25), 857-869.
https://scholar.uwindsor.ca/chemistrybiochemistrypub/337