Sandbox Reserved 1704: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| (One intermediate revision by one other user not shown) | |||
| Line 6: | Line 6: | ||
== General Structure == | == General Structure == | ||
Anaplastic lymphoma kinase is a homodimer, each monomer consisting of seven domains and two regions. These domains and regions are as follows: N-terminal region (NTR), two meprin–A-5 protein–receptor protein tyrosine phosphatase μ domains (MAM), low density lipoprotein receptor class A domain (LDL), tumor necrosis factor receptor-like domain (TNF), glycine rich region (GlyR), epidermal growth factor receptor-like domain (EGF), transmembrane α-helix (TMH), kinase domain <ref name="Reshetnyak">PMID:34819673</ref>. The structures of the N-terminal region, MAM, and LDL have not been determined. The glycine rich region is a part of the TNF domain. Only the TNF, GlyR, and EGF portions of ALK are required for ligand binding. All portions of anaplastic lymphoma kinase are located in the extracellular domain except for the transmembrane α-helix which is in the transmembrane region and the kinase domain that is located in the intracellular domain. [[Image:ALK_Domain_Outline.png|350 px|right|thumb|Figure 1. Outline of the domains and regions of anaplastic lymphoma kinase]] | Anaplastic lymphoma kinase is a homodimer, each monomer consisting of seven domains and two regions <ref name="Tongqing">PMID:34819665</ref>. These domains and regions are as follows: N-terminal region (NTR), two meprin–A-5 protein–receptor protein tyrosine phosphatase μ domains (MAM), low density lipoprotein receptor class A domain (LDL), tumor necrosis factor receptor-like domain (TNF), glycine rich region (GlyR), epidermal growth factor receptor-like domain (EGF), transmembrane α-helix (TMH), kinase domain <ref name="Reshetnyak">PMID:34819673</ref>. The structures of the N-terminal region, MAM, and LDL have not been determined. The glycine rich region is a part of the TNF domain. Only the TNF, GlyR, and EGF portions of ALK are required for ligand binding. All portions of anaplastic lymphoma kinase are located in the extracellular domain except for the transmembrane α-helix which is in the transmembrane region and the kinase domain that is located in the intracellular domain. [[Image:ALK_Domain_Outline.png|350 px|right|thumb|Figure 1. Outline of the domains and regions of anaplastic lymphoma kinase]] | ||
=== Ligand Binding=== | === Ligand Binding=== | ||
| Line 17: | Line 17: | ||
Anaplastic lymphoma kinase's involvement as a proto-oncogene in various types of cancers has made it a target for drug therapies for these types of cancers <ref name="Lewis">PMID:22734674</ref>. One therapeutic medication that has been increasingly used with high levels of success is Crizotinib. This medication was approved by the FDA in January of 2021 for the treatment of pediatric/young adult ALK-positive anaplastic large cell lymphoma. The treatment has an overall response rate of 90%. Crizotinib works by binding to the ATP binding site of the kinase domain <ref name="Sahu">PMID:24455567</ref>. Crizotinib binds preferentially to ATP in this region and therefore can effectively block the binding of ATP <ref name="Sahu" />. With the binding of ATP being blocked, the intercellular signaling cascade cannot begin which works to prevent the cancer from growing and spreading . | Anaplastic lymphoma kinase's involvement as a proto-oncogene in various types of cancers has made it a target for drug therapies for these types of cancers <ref name="Lewis">PMID:22734674</ref>. One therapeutic medication that has been increasingly used with high levels of success is Crizotinib. This medication was approved by the FDA in January of 2021 for the treatment of pediatric/young adult ALK-positive anaplastic large cell lymphoma. The treatment has an overall response rate of 90%. Crizotinib works by binding to the ATP binding site of the kinase domain <ref name="Sahu">PMID:24455567</ref>. Crizotinib binds preferentially to ATP in this region and therefore can effectively block the binding of ATP <ref name="Sahu" />. With the binding of ATP being blocked, the intercellular signaling cascade cannot begin which works to prevent the cancer from growing and spreading . | ||
<Structure load='Insert PDB code or filename here' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | |||
== References == | == References == | ||
