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View Entry | Protein kinases as cancer chemotherapy targets7004Protein kinases—enzymes that add phosphate groups to molecules—are cancer chemotherapy targets because they play significant roles in almost all aspects of cell function, are tightly regulated, and contribute to the development of cancer and other diseases if any alterations to their regulation occur. Genetic abnormalities affecting the c-Abl tyrosine kinase are linked to chronic myelogenous leukemia, a cancer of immature cells in the bone marrow. In the noncancerous form of the protein, binding of a myristoyl group to the kinase domain inhibits the activity of the protein until it is needed (top left shows the inactive form, top right shows the open and active form). The cancerous variant of the protein, called Bcr-Abl, lacks this autoinhibitory myristoyl group and is continually active (bottom). ATP is shown in green bound in the active site of the kinase.
Find these in the RCSB Protein Data Bank: c-Abl tyrosine kinase and regulatory domains (PDB entry 1OPL) and F-actin binding domain (PDB entry 1ZZP).
| | Public Note | | Three pictures of a large, multicolored blob. In the Inactive Abl, an orange semicircle holds the blob closed. In the Active Abl form, the orange tail has released the protein into an open position. In the Dysregulated Bcr-Abl form, the orange semicircle tail is replaced with a large orange circle labeled BCR that cannot hold the protein in the inactive form. | | | Internal Note | | From: Amy Wu
Sent: Thursday, February 1, 2024 4:20 PM
To: Bigler, Abbey (NIH/NIGMS) [C] ; Crowley, Rachel (NIH/NIGMS) [E]
Cc: Christine Zardecki
Subject: [EXTERNAL] RCSB PDB Content for the NIGMS Image and Video Gallery
Hi!
I hope all is well. Attached is a Google Folder link + Word document with all the requested images and information.
Link: https://drive.google.com/drive/folders/17GbO9ddzOn0UAifMihHDo6qAQdIQgE4r?usp=drive_link
Please feel free to email me with any questions.
Sincerely,
Amy
Funding Source: RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.
| | | Keywords | | CML | | | Source | | Amy Wu and Christine Zardecki, RCSB Protein Data Bank. | | | Date | | | | | Credit Line | | Allison Abel, Darlene R. Malave-Ramos, Bhavya Soni, Christopher Thai, Amy Wu-Wu, David S. Goodsell, Stephen K. Burley, and the RCSB Protein Data Bank. | | | Investigator | | In the normal protein, binding of the myristoyl group to the kinase domain inhibits the activity of the protein until it is needed. Bcr-Abl lacks this autoinhibitory myristoyl group and is continually active. ATP is shown in green bound in the active site of the kinase. | | | Record Type | | Illustration | | | Topic Area(s) | | ;#Injury and Illness;#Molecular Structures;# | | | Previous Uses | | | | | Status | | Active | |
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