Protein Energy Landscapes Determined by 5-Dimensional Crystallography

TL;DR

This paper introduces a novel five-dimensional crystallography method to directly determine energy barriers and landscapes of enzymes, linking structural data with kinetic barriers to deepen understanding of enzymatic reactions.

Contribution

It demonstrates how activation barriers can be derived solely from 5D crystallography, advancing the ability to analyze energy landscapes from structural data.

Findings

Determined activation barriers from 5D crystallography data.

Analyzed entropy and enthalpy contributions to barriers.

Linked structural states with energy barriers in enzymes.

Abstract

Free energy landscapes decisively determine the progress of enzymatically catalyzed reactions[1]. Time-resolved macromolecular crystallography unifies transient-state kinetics with structure determination [2-4] because both can be determined from the same set of X-ray data. We demonstrate here how barriers of activation can be determined solely from five-dimensional crystallography [5]. Directly linking molecular structures with barriers of activation between them allows for gaining insight into the structural nature of the barrier. We analyze comprehensive time series of crystal-lographic data at 14 different temperature settings and determine entropy and enthalpy contributions to the barriers of activation. 100 years after the discovery of X-ray scattering, we advance X-ray structure determination to a new frontier, the determination of energy landscapes.