User:Oluwapeluwa Sangoseni/Sandbox 1
From Proteopedia
(Difference between revisions)
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Thrombin alone does not cleave fibrinogen, however, and the process is far more complex than one would initially be led to believe. Several molecules also participate in the process, including 6P9U. Most research and data for this molecule has only been conducted and compiled very recently, as the protein data was only deposited in the PDB in mid-late 2019, so, compared to other well-known molecules, there is still quite a bit of work that can be done to learn more about it (3). 6P9U is the crystallized structure of the human thrombin mutant, W215A. Data about this molecule’s structure was compiled using X-ray diffraction, at a resolution of 3.3 Å. It is found in humans, and features an 8-carbon chain structure. It has a cyclic C2 symmetry, and is a hetero 4 mer with the stoichiometry equation A2B2, meaning it has 2 alpha sub units, and 2 beta sub units. In terms of its macromolecular content, it has a total structural weight of 141170.61 Daltons, and features an atom count of 9004. It has a residue count of 1216, with two unique protein chains. These two unique chains consist of two different prothrombin or coagulation factor II macromolecules, with different sequence lengths (31 and 273). Both are expressed by the gene F2. The macromolecule also contains two ligands that bind to it: a Zinc ion (Zn2+), and n-acetyl-D-glucosamine (C8H15NO6). 6P9U/W215A serves as a residue for a hydrolase, facilitating hydrolysis for thrombin, in which a molecule of water is used to break bonds between atoms or molecules. This allows for the required peptide bonds to be cleavedto enable the conversion of fibrinogen to fibrin (3). 6P9U/W215A’s functionality and uses extend to a wider variety of possibilities than just cleaving peptide bonds, however. | Thrombin alone does not cleave fibrinogen, however, and the process is far more complex than one would initially be led to believe. Several molecules also participate in the process, including 6P9U. Most research and data for this molecule has only been conducted and compiled very recently, as the protein data was only deposited in the PDB in mid-late 2019, so, compared to other well-known molecules, there is still quite a bit of work that can be done to learn more about it (3). 6P9U is the crystallized structure of the human thrombin mutant, W215A. Data about this molecule’s structure was compiled using X-ray diffraction, at a resolution of 3.3 Å. It is found in humans, and features an 8-carbon chain structure. It has a cyclic C2 symmetry, and is a hetero 4 mer with the stoichiometry equation A2B2, meaning it has 2 alpha sub units, and 2 beta sub units. In terms of its macromolecular content, it has a total structural weight of 141170.61 Daltons, and features an atom count of 9004. It has a residue count of 1216, with two unique protein chains. These two unique chains consist of two different prothrombin or coagulation factor II macromolecules, with different sequence lengths (31 and 273). Both are expressed by the gene F2. The macromolecule also contains two ligands that bind to it: a Zinc ion (Zn2+), and n-acetyl-D-glucosamine (C8H15NO6). 6P9U/W215A serves as a residue for a hydrolase, facilitating hydrolysis for thrombin, in which a molecule of water is used to break bonds between atoms or molecules. This allows for the required peptide bonds to be cleavedto enable the conversion of fibrinogen to fibrin (3). 6P9U/W215A’s functionality and uses extend to a wider variety of possibilities than just cleaving peptide bonds, however. | ||
- | W215 along with E217 and E192, are residues that work together to regulate thrombin’s activity. Specifically, W215 is responsible for maintaining the allosteric equilibrium of thrombin’s closed and open conformations, which would maintain thrombin’s catalytic activity, bycontrolling the rate of transition between the two forms, if need be (4). It does this by use of hydrophobic interactions with the benzene ring portion of thrombin’s F227 residue. This keeps the enzyme’s active site open, which causes the rate at which the open conformation closes to decrease. This is because thrombin’s zymogen, which is the inactive, immature form of the enzyme, is the more common form of the enzyme when it is in its closed conformation. By opening, the zymogen matures along with it, being converted into the active and mature form. It was discovered that W215A functions similarly to W215, as if you were to replace W215 with W215A, the rate of transition between the two conformations would still be maintained, almost as if it were still W215. If W215 or W215A were to be removed completely, or its hydrophobic interaction with F227 is otherwise disrupted, then the rate at which thrombin’s conformation closes would be increased, and thrombin’s activity would be decreased, as the equilibrium between the closed and open conformations are responsible for the enzyme’s activity (4). | + | W215, along with E217 and E192, are residues that work together to regulate thrombin’s activity. Specifically, W215 is responsible for maintaining the allosteric equilibrium of thrombin’s closed and open conformations, which would maintain thrombin’s catalytic activity, bycontrolling the rate of transition between the two forms, if need be (4). It does this by use of hydrophobic interactions with the benzene ring portion of thrombin’s F227 residue. This keeps the enzyme’s active site open, which causes the rate at which the open conformation closes to decrease. This is because thrombin’s zymogen, which is the inactive, immature form of the enzyme, is the more common form of the enzyme when it is in its closed conformation. By opening, the zymogen matures along with it, being converted into the active and mature form. It was discovered that W215A functions similarly to W215, as if you were to replace W215 with W215A, the rate of transition between the two conformations would still be maintained, almost as if it were still W215. If W215 or W215A were to be removed completely, or its hydrophobic interaction with F227 is otherwise disrupted, then the rate at which thrombin’s conformation closes would be increased, and thrombin’s activity would be decreased, as the equilibrium between the closed and open conformations are responsible for the enzyme’s activity (4). |
== Relevance == | == Relevance == |
Revision as of 01:53, 28 April 2020
6P9U, Crystal Structure of Human Thrombin Mutant W215A
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References
- ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
- ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644