About the laboratory
Environmental factors on biomolecule structure
and function
The threat of PM2.5 to the global ecological environment and human health cannot be ignored. Although the relationship between PM2.5 and major diseases such as respiratory, cardiovascular, neurodegenerative, and cancer has been confirmed, the basic mechanism of its pathogenicity has not been fully clarified. Biomolecules in the body are exposed to environmental factors such as biotoxic PM2.5. How the structural and functional mutations occur after the invasion has not yet been fully grasped, resulting in the current humans have no specific methods and strategies on how to reduce or prevent various diseases caused by PM2.5.
The chemical composition and structure of a biomolecular system often have a decisive influence on its biological function. When a disease occurs, it is usually accompanied by changes in the chemical composition and structure. Only when we have a deep understanding and mastery of these structural variations, their dynamics, thermodynamics and other physical and chemical properties from the molecular level, can we develop active prevention and treatment of these diseases caused by structural variations. .
In view of this, in addition to in-depth exploration of the basic physical and chemical properties of aerosol itself, this laboratory is also committed to in-depth understanding of how important biomolecules in the human body undergo structural and functional changes due to environmental factors. Since blood is the most important substance that circulates throughout the body through the system and is responsible for transporting oxygen to sustain life, hemoglobin is currently the laboratory's first choice for understanding the impact of environmental factors on the structure and function of biomolecules.
Normal adult hemoglobin is a tetramer composed of α and β two subunits, α2β2. Only when the proportions of the sub-units and their arrangement in space are correct, hemoglobin can accurately perform the biological function of transporting oxygen in the body. Once the ratio of heme subunits changes or the tertiary or even quaternary structure of the globulin changes, it will lead to defects in its oxygen-carrying function and the occurrence of blood diseases, such as sickle-type anemia and thalassemia. .
Since cysteine is highly biologically active, it is one of the most vulnerable sites to be attacked by environmental factors. In order to understand the importance of cysteine in maintaining the structural stability of hemoglobin, and the reaction mechanism of structural destruction when it reacts with organic mercury, we discussed the organic mercury compound PMB (p-hydroxymercuribenzoate) and cysteine on hemoglobin A reaction that loosens the structure of hemoglobin and breaks it down into subunit disassembly. Human hemoglobin is a structurally stable tetrameric protein composed of two α monomers and two β monomers. It has three different cysteine residues distributed at the βCys93、αCys104、βCys112 positions.
In this work, a matrix-assisted laser desorption free time-of-flight mass spectrometer was used to observe the reactivity, reaction sequence and binding strength of cysteine residues at different positions with PMB, and then deduced the separation of hemoglobin tetramers into monomers The possible reaction mechanism and the pivotal role played by the cysteine residues at various positions in maintaining the structure of hemoglobin tetramers. This work explores the process of post-translational modification (post-translational modification) after the highly active cysteine in protein is disturbed by environmental factors.
This work provides further insights on the molecular basis for understanding how environmental factors can cause changes or loss of the structure and function of biomolecules. The purpose of this research direction is to develop drugs and methods that can effectively treat blood diseases and apply them to prevent or adjust new biological medical treatments or new drug developments that cause blood oxygen dysfunction caused by environmental factors.
Reference works
* Wei-Ren Chen, Youqing Yu, Muhammad Zulfajri, Ping-Cheng Lin, Zhong-Hang Wu, Meng-Sin Chen and Chia C. Wang*, Phthalide Derivatives from Angelica Sinensis Decrease Oxygen Affinity of Hemoglobin: A New Allosteric-Modulating Mechanism and Potential Use as 2,3-BPG Substitutes, Sci. Rep., accepted (2017).
* Heng-I Kan, Yi-Ying Chen and Chia C. Wang*, Subunit disassembly of human hemoglobin unravels the site-specific roles of its cysteine residues, J. Phys. Chem. B, 117, 9831 (2013)