Search for allosteric disulfide bonds in NMR structures

Area of Science:

• Structural Biology
• Biochemistry
• Computational Biology

Background:

• Allosteric disulfide bonds are crucial for regulating protein function through their formation and breakage.
• These bonds typically adopt a -RHStaple configuration, determined by the signs of five chi angles.

Purpose of the Study:

• To compare and contrast the configuration and strain energy of disulfide bonds across various protein structure datasets.
• To investigate discrepancies in disulfide bond representation between NMR and X-ray crystallography.

Main Methods:

• Analysis of disulfide bond configurations and strain energies in large datasets of NMR and X-ray protein structures.
• Comparison of strain energy distributions and disulfide bond types between NMR and X-ray structures.
• Evaluation of specific disulfide bond configurations, such as -LHStaple, in different structural models.

Main Results:

• Disulfide bonds in NMR structures exhibit approximately twice the mean dihedral strain energy compared to those in X-ray structures.
• All twenty types of disulfide bonds showed higher energies in NMR structures than in X-ray structures.
• The -LHStaple configuration, rare in X-ray structures, is associated with high potential energy and short alpha-carbon distances in NMR structures.

Conclusions:

• Significant differences exist in disulfide bond strain energy and configuration between NMR and X-ray protein structure models.
• The functional relevance of different disulfide bond configurations, such as -RHStaple versus -LHStaple, remains an open question, particularly in proteins like HIV gp120.
• Discrepancies highlight the importance of considering the structural model type when interpreting disulfide bond roles in protein function.