Proteins in organic solvents

doi:10.1016/S0959-440X(01)00278-0

Current Opinion in Structural Biology

Volume 11, Issue 6, 1 December 2001, Pages 761-764

https://doi.org/10.1016/S0959-440X(01)00278-0 Get rights and content

Abstract

Catalysis in organic solvents and the mapping of protein surfaces using multiple solvent crystal structures are two rapidly developing areas of research. Recent advances include the study of protein folding and stability in different solvents, and the demonstration that it is possible to qualitatively rank the affinities of protein binding sites for a given organic solvent using the multiple solvent crystal structures method.

Introduction

The concept that proteins should remain folded and active in organic solvents is counterintuitive. After all, proteins evolved in an aqueous milieu and have ubiquitously incorporated water in their folding, three-dimensional structure, function and dynamics. Structural studies have implicated water molecules in protein architecture and catalysis, and in the specificity, cooperativity and thermodynamics of ligand binding [1•]. Structural work has gained insight from the study of water–protein interactions through a variety of different methods that stress the uniqueness of water in its properties as a solvent and a key player in biological processes [2]. Yet, it is well known that proteins are stable in some organic solvents and even multicomponent enzymes have been shown to retain catalytic activity, albeit at significantly lower levels than in water [3]. Work on enzymes in organic solvents began in the first part of the twentieth century, but only in the past two decades has the field developed into a robust and powerful area of research [4]. It currently spans the fields of enzymology, synthetic organic chemistry and, most recently, structural biology. This review focuses on the latest advances contributing to the understanding of the structure of proteins in organic solvents. For a focus on the chemistry that can be catalyzed by enzymes in aqueous and nonaqueous media, the reader is referred to a series of review articles that appeared recently in the journal Nature 5., 6., 7., 8•., 9., 10., 11..

Section snippets

Protein catalysis in organic solvents: structural aspects

It is well known that the catalytic activity of enzymes in organic solvents is far lower than in water [12]. Many of the advances in the past few years have contributed to both the elucidation of the underlying reasons for this difference in activity and the discovery of remedies to overcome the resulting limitations [8•]. From a biochemist's viewpoint, there is such a large divide between the behavior of proteins in aqueous solution and that in organic solvents that the distinctions between

Multiple solvent crystal structures

The question of whether the different chemical reactions and selectivity of enzymes in organic solvents resulted from a modified active site geometry provided the initial motivation for solving the crystal structure of an enzyme in organic solvents. The first structure resulted from an interest in observing the features of catalytically active subtilisin Carlsburg in neat acetonitrile [35]. This structure and others that followed established that proteins in several different organic solvents,

Conclusions

Much of the work done in the past three years to understand and enhance enzyme catalysis in organic solvents has also elucidated the effects of solvents on protein structure. For instance, the study of protein folding in organic solvents, the use of ligands and lyoprotectants to avoid protein denaturation during lyophilization, and the demonstration that the structure of proteins in organic solvents can be controlled by previous history all contribute to understanding structure in organic

Acknowledgements

Carla Mattos is a recipient of the Burroughs Wellcome Fund New Investigator Award in the Basic Pharmacological Sciences.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

• of special interest
•• of outstanding interest

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ReviewProteins in organic solvents

Abstract

Introduction

Section snippets

Protein catalysis in organic solvents: structural aspects

Multiple solvent crystal structures

Conclusions

Acknowledgements

References and recommended reading

Trends Biotechnol

Trends Biotechnol

J Am Soc Mass Spectrom

Biochim Biophys Acta

Biochim Biophys Acta

Enzyme Microb Technol

Biochem Biophys Res Commun

Solvent structure

Hydration Processes in Biology

Aromatic hydroxylation catalyzed by toluene 4-monooxygenase in organic solvent/aqueous buffer mixtures

Appl Biochem Biotechnol

Enabling the chemistry of life

Nature

Correction: enabling the chemistry of life

Nature

Enzymes for chemical synthesis

Nature

Improving enzymes by using them in organic solvents

Nature

Modular enzymes

Nature

Combinatorial and computational challenges for biocatalyst design

Nature

Industrial biocatalysis today and tomorrow

Nature

Optimizing the salt-induced activation of enzymes in organic solvents: effects of lyophilization time and water content

Biotechnol Bioeng

Striking activation of oxidative enzymes suspended in nonaqueous media

Proc Natl Acad Sci USA

Structure of lysozyme dissolved in neat organic solvents as assessed by NMR and CD spectroscopies

Biotechnol Bioeng

Methanol-induced conformations of myoglobin at pH 4.0

Biochemistry

Review
Proteins in organic solvents