Sandbox GGC15
From Proteopedia
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== Structure == | == Structure == | ||
Human topo 1 is composed of 765 amino acids <ref name="Redinbo" />. The enzyme consist of 4 regions which are the NH2-terminal, core, linker, and COOH-terminal domains<ref name="Redinbo" />. The NH2-terminal is approximately 210 residues long, it is highly charged, disordered, and contains few hydrophobic amino acids<ref name="Redinbo" />. The COOH-terminal domain is made up of residues 713 to 765 and contains the important amino aside Tyrosine 223<ref name="Redinbo"/>. The location of the active site is at this amino acid<ref name="Redinbo" />. | Human topo 1 is composed of 765 amino acids <ref name="Redinbo" />. The enzyme consist of 4 regions which are the NH2-terminal, core, linker, and COOH-terminal domains<ref name="Redinbo" />. The NH2-terminal is approximately 210 residues long, it is highly charged, disordered, and contains few hydrophobic amino acids<ref name="Redinbo" />. The COOH-terminal domain is made up of residues 713 to 765 and contains the important amino aside Tyrosine 223<ref name="Redinbo"/>. The location of the active site is at this amino acid<ref name="Redinbo" />. | ||
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== Active Site == | == Active Site == | ||
| - | + | Topo 1 reduces stress in DNA by causing a transient single strand nick in the the DNA helix<ref name="Staker" />. This nick enables the cut to rotate around its intact complement, thus eliminating proximal supercoils<ref name="Staker" />. | |
| - | The active site is catalytic and | + | |
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| + | The active site of Topo 1 is catalytic and it is the location where the nicking or cutting occurs<ref name="Redinbo" />. The nicking occurs from the trans-esterification of Tyr-723 at a DNA phophodiester bond forming a 3�-phosphotyrosine covalent enzyme–DNA complex <ref name="Staker" />. After the DNA is relaxed, the covalent intermediate is reversed when the released 5�-OH of the broken strand reattacks the phosphotyrosine intermediate in a second transesterification reaction<ref name="Staker" />. | ||
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== Relevance == | == Relevance == | ||
Many anticancer drugs target topo 1 enzymes. | Many anticancer drugs target topo 1 enzymes. | ||
| - | == | + | == Mutations == |
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | ||
Revision as of 21:20, 27 April 2021
DNA TOPOISOMERASE I
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References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin AB Jr, Stewart L. The mechanism of topoisomerase I poisoning by a camptothecin analog. Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15387-92. Epub 2002 Nov 8. PMID:12426403 doi:10.1073/pnas.242259599
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Redinbo MR, Stewart L, Kuhn P, Champoux JJ, Hol WG. Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA. Science. 1998 Mar 6;279(5356):1504-13. PMID:9488644
