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Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):481-91. doi: 10.1107/S1399004713028812. Epub 2014 Jan 29.

Factors correlating with significant differences between X-ray structures of myoglobin.

Author information

1
BioChemComp Inc., 543 Sagamore Avenue, Teaneck, NJ 07666, USA.
2
Department of Molecular Physiology and Biological Physics, University of Virginia, 1340 Jefferson Park Avenue, Jordan Hall, Room 4223, Charlottesville, VA 22908, USA.
3
LH Baker Center for Bioinformatics and Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, 112 Office and Lab Bldg, Ames, IA 50011-3020, USA.

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.

KEYWORDS:

bioinformatics; computation; conformation; function; proteins; validation

PMID:
24531482
PMCID:
PMC3940193
DOI:
10.1107/S1399004713028812
[Indexed for MEDLINE]
Free PMC Article

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