# Protein Structure Determination by Racemic and Quasi‐Racemic X‐Ray Crystallography

## TL;DR

This paper explains how using racemic and quasi-racemic protein mixtures improves X-ray crystallography for determining protein structures.

## Contribution

The paper highlights the novel use of racemic and quasi-racemic protein mixtures to enhance crystallization and simplify structure determination.

## Key findings

- Racemic protein mixtures form centrosymmetric crystals with higher success rates.
- Quasi-racemic mixtures also facilitate high-quality crystal formation.
- These methods simplify solving protein structures using X-ray crystallography.

## Abstract

This perspective essay recounts fundamental aspects of two forms of racemic protein crystallography, techniques that significantly enhance the success rate for determining protein molecular structures by X‐ray diffraction. Crystallization from a racemic mixture of protein enantiomers, i.e., the natural chirality L‐protein and its D‐protein enantiomer, gives highly ordered centrosymmetric crystals with a success rate much greater than for the L‐protein alone and even facilitates the crystallization of L‐protein molecules proven to be recalcitrant to crystallization by conventional methods. X‐ray reflections from such centrosymmetric racemic protein crystals have quantized phases, greatly simplifying solution of protein structures by direct methods and giving high‐quality electron density maps. Quasi‐racemic mixtures of protein isomorphs (proteins with mirror image shapes that are not true chemical enantiomers) also strongly facilitate the formation of diffraction‐quality crystals. D‐protein molecules are prepared by total synthesis based on modern chemical ligation methods. Examples selected from the literature will be highlighted to illustrate the application and utility of racemic crystallography for the elucidation of protein structures.

Racemic mixtures of protein enantiomers facilitate formation of diffraction‐quality crystals in centrosymmetric space groups that have quantized phases which simplify structure solution. Quasi‐racemic mixtures of a protein and its mirror image isomorph similarly facilitate formation of highly ordered crystals. Racemic and quasi‐racemic X‐ray crystallography enable elucidation of structures of recalcitrant proteins and protein complexes.© 2026 WILEY‐VCH GmbH