Underlying features for the enhanced electrostatic strength of the extremophilic malate dehydrogenase interface salt-bridge compared to the mesophilic one

Article Type

Research Article

Publication Title

Journal of Biomolecular Structure and Dynamics

Abstract

Malate dehydrogenase (MDH) exists in multimeric form in normal and extreme solvent conditions where residues of the interface are involved in specific interactions. The interface salt-bridge (ISB) and its microenvironment (ME) residues may have a crucial role in the stability and specificity of the interface. To gain insight into this, we have analyzed 218 ISBs from 42 interfaces of 15 crystal structures along with their sequences. Comparative analyses demonstrate that the ISB strength is ∼30 times greater in extremophilic cases than that of the normal one. To this end, the interface residue propensity, ISB design and pair selection, and ME-residue’s types, i.e., type-I and type-II, are seen to be intrinsically involved. Although Type-I is a common type, Type-II appears to be extremophile-specific, where the net ME-residue count is much lower with an excessive net ME-energy contribution, which seems to be a novel interface compaction strategy. Furthermore, the interface strength can be enhanced by selecting the desired mutant from the net-energy profile of all possible mutations of an unfavorable ME-residue. The study that applies to other similar systems finds applications in protein–protein interaction and protein engineering. Communicated by Ramaswamy H. Sarma.

DOI

https://10.1080/07391102.2023.2295972

Publication Date

1-1-2023

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