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.
Copyright Owner
International Union of Crystallography
Copyright Date
2014
Language
en
File Format
application/pdf
Recommended Citation
Rashin, Alexander A.; Domagalski, Marcin J.; Zimmermann, Michael T.; Minor, Wladek; Chruszcz, Maksymilian; and Jernigan, Robert L., "Factors correlating with significant differences between X-ray structures of myoglobin" (2014). Biochemistry, Biophysics and Molecular Biology Publications. 162.
https://lib.dr.iastate.edu/bbmb_ag_pubs/162
Included in
Biochemistry Commons, Bioinformatics Commons, Biophysics Commons, Molecular Biology Commons, Structural Biology Commons
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.