Predictability of weak binding from X-ray crystallography: inhaled anesthetics and myoglobin.

Abstract

Xenon and dichloromethane are inhalational anesthetic agents whose binding to myoglobin has been demonstrated by X-ray crystallography. We explore the thermodynamic significance of such binding using differential scanning calorimetry, circular dichroism spectroscopy, and hydrogen-tritium exchange measurements to study the effect of these agents on myoglobin folding stability. Though specific binding of these anesthetics might be expected to stabilize myoglobin against unfolding, dichloromethane actually destabilized myoglobin at all examined concentrations of this anesthetic (15, 40, and 200 mM). On the other hand, xenon (1 atm) stabilized myoglobin. Thus, dichloromethane and xenon have opposite effects on myoglobin stability despite localization in comparably folded X-ray crystallographic structures. These results suggest a need for solution measurements to complement crystallography if the consequences of weak binding to proteins are to be appreciated. Study holds ProTherm entries: 11758, 11759, 11760, 11761, 11762, 11763 Extra Details: inhalational anesthetic agents; folding stability; dichloromethane; xenon

Submission Details

ID: 2zgeKdxM4

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:43 p.m.

Version: 1

Publication Details
Tanner JW;Johansson JS;Liebman PA;Eckenhoff RG,Biochemistry (2001) Predictability of weak binding from X-ray crystallography: inhaled anesthetics and myoglobin. PMID:11305924
Additional Information

Study Summary

Number of data points 6
Proteins Myoglobin ; Myoglobin
Unique complexes 1
Assays/Quantities/Protocols Experimental Assay: Tm buffers:dichloromethane: 200 mM ; Experimental Assay: Tm buffers:dichloromethane: 40 mM ; Experimental Assay: Tm buffers:dichloromethane: 0 mM ; Experimental Assay: Tm buffers:dichloromethane: 200 mM ; Experimental Assay: Tm buffers:dichloromethane: 40 mM ; Experimental Assay: Tm buffers:dichloromethane: 0 mM
Libraries Mutations for sequence GLSDGEWQQVLNVWGKVEADIAGHGQEVLIRLFTGHPETLEKFDKFKHLKTEAEMKASEDLKKHGTVVLTALGGILKKKGHHEAELKPLAQSHATKHKIPIKYLEFISDAIIHVLHSKHPGDFGADAQGAMTKALELFRNDIAAKYKELGFQG

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Myoglobin P68083 MYG_EQUBU
100.0 Myoglobin P68082 MYG_HORSE
91.6 Myoglobin P02181 MYG_INIGE
92.2 Myoglobin P02169 MYG_LEPMU
90.9 Myoglobin P02166 MYG_PERPO
90.9 Myoglobin P02189 MYG_PIG
90.8 Myoglobin Q0KIY1 MYG_BALBO
90.8 Myoglobin Q0KIY2 MYG_BALED
90.8 Myoglobin P02177 MYG_ESCRO
90.3 Myoglobin P02183 MYG_MESCA
90.3 Myoglobin Q0KIY0 MYG_MESST
90.3 Myoglobin P02167 MYG_NYCCO
90.3 Myoglobin P02165 MYG_TUPGL
90.9 Myoglobin P11343 MYG_LUTLU
90.3 Myoglobin P02163 MYG_ROUAE
90.1 Myoglobin P02178 MYG_MEGNO