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Functional Prediction from Conformational Dynamics of Glycated and Glutathionylated HbE and HbD Punjab


Affiliations
1 Clinical Proteomics Unit, Division of Molecular Medicine, St John’s Research Institute, St John’s National Academy of Health Sciences, Bengaluru 560 034, India
2 Manipal Hospital, Old Airport Road, Bengaluru 560 017, India
 

Glycation and glutathionylation are important posttranslational modifications (PTMs) of human haemoglobin that act as biomarkers of diabetes mellitus and oxidative stress. These PTMs perturb the function of normal haemoglobin. However, the structure–function correlation of these PTMs of genetically modified haemoglobin remained unexplored. Using hydrogen/ deuterium exchange mass spectrometry, we studied the conformational dynamics of glycated and glutathionylated forms of two haemoglobin variants, HbE and HbD Punjab. Like glycated and glutathionylated normal haemoglobin, these PTMs of HbE were expected to have increased oxygen affinity. However, for HbD Punjab, glycation was predicted to have decreased oxygen affinity whereas glutathionylation to have increased oxygen affinity.

Keywords

Glutathionylation, HbE, HbD Punjab, Glycation, Post-Translational Modifications, Structure–Function Correlation.
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  • Functional Prediction from Conformational Dynamics of Glycated and Glutathionylated HbE and HbD Punjab

Abstract Views: 376  |  PDF Views: 77

Authors

Sreekala Narayanan
Clinical Proteomics Unit, Division of Molecular Medicine, St John’s Research Institute, St John’s National Academy of Health Sciences, Bengaluru 560 034, India
Boby Mathew
Clinical Proteomics Unit, Division of Molecular Medicine, St John’s Research Institute, St John’s National Academy of Health Sciences, Bengaluru 560 034, India
Bindu Y. Srinivasu
Clinical Proteomics Unit, Division of Molecular Medicine, St John’s Research Institute, St John’s National Academy of Health Sciences, Bengaluru 560 034, India
Monita Muralidharan
Clinical Proteomics Unit, Division of Molecular Medicine, St John’s Research Institute, St John’s National Academy of Health Sciences, Bengaluru 560 034, India
Vijay Bhat
Manipal Hospital, Old Airport Road, Bengaluru 560 017, India
Amit Kumar Mandal
Clinical Proteomics Unit, Division of Molecular Medicine, St John’s Research Institute, St John’s National Academy of Health Sciences, Bengaluru 560 034, India

Abstract


Glycation and glutathionylation are important posttranslational modifications (PTMs) of human haemoglobin that act as biomarkers of diabetes mellitus and oxidative stress. These PTMs perturb the function of normal haemoglobin. However, the structure–function correlation of these PTMs of genetically modified haemoglobin remained unexplored. Using hydrogen/ deuterium exchange mass spectrometry, we studied the conformational dynamics of glycated and glutathionylated forms of two haemoglobin variants, HbE and HbD Punjab. Like glycated and glutathionylated normal haemoglobin, these PTMs of HbE were expected to have increased oxygen affinity. However, for HbD Punjab, glycation was predicted to have decreased oxygen affinity whereas glutathionylation to have increased oxygen affinity.

Keywords


Glutathionylation, HbE, HbD Punjab, Glycation, Post-Translational Modifications, Structure–Function Correlation.

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DOI: https://doi.org/10.18520/cs%2Fv118%2Fi5%2F722-727