Factors correlating with significant differences between X-ray structures of myoglobin
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 difference...
Main Authors: | , , , , , |
---|---|
Format: | Text |
Language: | English |
Published: |
Iowa State University Digital Repository
2014
|
Subjects: | |
Online Access: | https://lib.dr.iastate.edu/bbmb_ag_pubs/162 https://lib.dr.iastate.edu/cgi/viewcontent.cgi?article=1170&context=bbmb_ag_pubs |
id |
ftiowastateuniv:oai:lib.dr.iastate.edu:bbmb_ag_pubs-1170 |
---|---|
record_format |
openpolar |
spelling |
ftiowastateuniv:oai:lib.dr.iastate.edu:bbmb_ag_pubs-1170 2023-05-15T18:26:52+02:00 Factors correlating with significant differences between X-ray structures of myoglobin Rashin, Alexander A Domagalski, Marcin J Zimmermann, Michael T Minor, Wladek Chruszcz, Maksymilian Jernigan, Robert L 2014-02-01T08:00:00Z application/pdf https://lib.dr.iastate.edu/bbmb_ag_pubs/162 https://lib.dr.iastate.edu/cgi/viewcontent.cgi?article=1170&context=bbmb_ag_pubs en eng Iowa State University Digital Repository https://lib.dr.iastate.edu/bbmb_ag_pubs/162 https://lib.dr.iastate.edu/cgi/viewcontent.cgi?article=1170&context=bbmb_ag_pubs Biochemistry, Biophysics and Molecular Biology Publications Biochemistry Bioinformatics Biophysics Molecular Biology Structural Biology text 2014 ftiowastateuniv 2021-08-28T22:47:45Z 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. Text Sperm whale Digital Repository @ Iowa State University Holo ENVELOPE(9.954,9.954,63.343,63.343) |
institution |
Open Polar |
collection |
Digital Repository @ Iowa State University |
op_collection_id |
ftiowastateuniv |
language |
English |
topic |
Biochemistry Bioinformatics Biophysics Molecular Biology Structural Biology |
spellingShingle |
Biochemistry Bioinformatics Biophysics Molecular Biology Structural Biology Rashin, Alexander A Domagalski, Marcin J Zimmermann, Michael T Minor, Wladek Chruszcz, Maksymilian Jernigan, Robert L Factors correlating with significant differences between X-ray structures of myoglobin |
topic_facet |
Biochemistry Bioinformatics Biophysics Molecular Biology Structural Biology |
description |
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. |
format |
Text |
author |
Rashin, Alexander A Domagalski, Marcin J Zimmermann, Michael T Minor, Wladek Chruszcz, Maksymilian Jernigan, Robert L |
author_facet |
Rashin, Alexander A Domagalski, Marcin J Zimmermann, Michael T Minor, Wladek Chruszcz, Maksymilian Jernigan, Robert L |
author_sort |
Rashin, Alexander A |
title |
Factors correlating with significant differences between X-ray structures of myoglobin |
title_short |
Factors correlating with significant differences between X-ray structures of myoglobin |
title_full |
Factors correlating with significant differences between X-ray structures of myoglobin |
title_fullStr |
Factors correlating with significant differences between X-ray structures of myoglobin |
title_full_unstemmed |
Factors correlating with significant differences between X-ray structures of myoglobin |
title_sort |
factors correlating with significant differences between x-ray structures of myoglobin |
publisher |
Iowa State University Digital Repository |
publishDate |
2014 |
url |
https://lib.dr.iastate.edu/bbmb_ag_pubs/162 https://lib.dr.iastate.edu/cgi/viewcontent.cgi?article=1170&context=bbmb_ag_pubs |
long_lat |
ENVELOPE(9.954,9.954,63.343,63.343) |
geographic |
Holo |
geographic_facet |
Holo |
genre |
Sperm whale |
genre_facet |
Sperm whale |
op_source |
Biochemistry, Biophysics and Molecular Biology Publications |
op_relation |
https://lib.dr.iastate.edu/bbmb_ag_pubs/162 https://lib.dr.iastate.edu/cgi/viewcontent.cgi?article=1170&context=bbmb_ag_pubs |
_version_ |
1766208838530236416 |