On the Sensitivity of Protein Data Bank Normal Mode Analysis: An Application to GH10 Xylanases

TL;DR

This study evaluates the sensitivity of normal mode analysis on protein structures, specifically analyzing how different conformations of a key tryptophan residue influence flexibility spectra and enzyme classification.

Contribution

It demonstrates how conformational variations in a conserved residue impact normal mode analysis results and enzyme flexibility characterization.

Findings

Different tryptophan conformations lead to distinct flexibility spectra.

Sidechain orientation affects the motility of a distant enzyme region.

Normal mode analysis sensitivity varies with residue conformation.

Abstract

Protein data bank entries obtain distinct, reproducible flexibility characteristics determined by normal mode analyses of their three dimensional coordinate files. We study the effectiveness and sensitivity of this technique by analyzing the results on one class of glycosidases: family 10 xylanases. A conserved tryptophan that appears to affect access to the active site can be in one of two conformations according to X-ray crystallographic electron density data. The two alternate orientations of this active site tryptophan lead to distinct flexibility spectra, with one orientation thwarting the oscillations seen in the other. The particular orientation of this sidechain furthermore affects the appearance of the motility of a distant, C terminal region we term the mallet. The mallet region is known to separate members of this family of enzymes into two classes.