Modeling for tertiary structure of globin chain in Hemoglobin Suan-Dok disorder

Abstract

Hemoglobinopathies are an important inherited disorder with a high prevalence in Southeast Asia. Hemoglobin Suan-Dok is an example of a hemoglobinopathy that was first identified and described in Thailand. It has been identified as an unstable hemoglobin variant associated with alpha-thalassemia. The role of the hemoglobin instability in Hb Suan-Dok in the altered red cell morphology in comparison to the thalassemia-like deficit of alpha globin mRNA has not been entirely resolved and needs additional structural study for clarification. In this study the amino acid sequence of human alpha globin was extracted using ExPASY and compared with that obtained from the Hb Suan-Dok disorder. The derived sequences, alpha globin chains in both the normal and Hb Suan-Dok disorder, were used for further investigation of the tertiary structures. Modeling these proteins for the tertiary structure was performed using the CPHmodels 2.0 Server. For comparison the tertiary structure of human alpha globin chains in normal and hemoglobin Suan-Dok are calculated and presented. Based on this information, there was no significant difference between the predicted alpha globin tertiary structures of normal hemoglobin and Hb Suan-Dok. Therefore, from this study we can state that the tertiary structure of alpha globin is not significantly affected by the mutation in the Hb Suan-Dok disorder and that the effect of this hemoglobin abnormality may be silent. The data suggests that the thalassemic defect associated with the Suan-Dok mutation results from another unidentified process rather than the structural aberration and that the finding of a thalassemic picture might be due to another undetectable inherited hemoglobin disorder.