Campus Units

Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of, Baker Center for Bioinformatics and Biological Statistics

Document Type

Article

Publication Version

Published Version

Publication Date

2-2014

Journal or Book Title

Acta Crystallographica Section D

Volume

70

Issue

2

First Page

481

Last Page

491

DOI

10.1107/S1399004713028812

Abstract

Validation of general ideas about the origins of conformational differences in proteins is critical in order to arrive at meaningful functional insights. Here, principal component analysis (PCA) and distance difference matrices are used to validate some such ideas about the conformational differences between 291 myoglobin structures from sperm whale, horse and pig. Almost all of the horse and pig structures form compact PCA clusters with only minor coordinate differences and outliers that are easily explained. The 222 whale structures form a few dense clusters with multiple outliers. A few whale outliers with a prominent distortion of the GH loop are very similar to the cluster of horse structures, which all have a similar GH-loop distortion apparently owing to intermolecular crystal lattice hydrogen bonds to the GH loop from residues near the distal histidine His64. The variations of the GH-loop coordinates in the whale structures are likely to be owing to the observed alternative intermolecular crystal lattice bond, with the change to the GH loop distorting bonds correlated with the binding of specific ‘unusual’ ligands. Such an alternative intermolecular bond is not observed in horse myoglobins, obliterating any correlation with the ligands. Intermolecular bonds do not usually cause significant coordinate differences and cannot be validated as their universal cause. Most of the native-like whale myoglobin structure outliers can be correlated with a few specific factors. However, these factors do not always lead to coordinate differences beyond the previously determined uncertainty thresholds. The binding of unusual ligands by myoglobin, leading to crystal-induced distortions, suggests that some of the conformational differences between the apo and holo structures might not be ‘functionally important’ but rather artifacts caused by the binding of ‘unusual’ substrate analogs. The causes of P6 symmetry in myoglobin crystals and the relationship between crystal and solution structures are also discussed.

Comments

This article is published as Rashin, A. A., Domagalski, M. J., Zimmermann, M. T., Minor, W., Chruszcz, M. and Jernigan, R. L. (2014), Factors correlating with significant differences between X-ray structures of myoglobin. Acta Crystallographica Section D, 70: 481–491. doi: 10.1107/S1399004713028812. Posted with permission.

Copyright Owner

International Union of Crystallography

Language

en

File Format

application/pdf

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