# AI Drug Design - Serine-protein kinase ATM
###### tags: `NYCU`

## Motivation
- Target: Diabetes Mellitus
- 家族病史
- 工作
- Drug
- insulin analogues
- GLP1
- SGLT2 Inhibitor
- Paper:
- ATM Protein Kinase Signaling, Type 2 Diabetes and Cardiovascular Disease.
- ATM Protein Kinase: Old and New Implications in Neuronal Pathways and Brain Circuitry.

## Introduction
- Serine-protein kinase ATM (絲氨酸蛋白激酶), sympol ATM.
- a member of the phosphatidylinositol-3 kinase-like protein kinase (PIKK) family.
- approximately 350 kDa.
- From ATM Gene
- ataxia telangiectasia mutated 共濟失調微血管擴張突變隱性疾病
- prevalence is of 1:40,000 to 1:100,000
- chromosome 11q22-23

## Strcuture
- KD domain.
- An N-terminal substrate-binding domain (HEAT repeat domain), which binds to some known substrates such as NBS1, p53, and BRCA1 and whose deletion inactivates the protein.

## Function
- 神經系統 Central nervous system (CNS)
- DNA修復 (DNA damage response (DDR))
- 調節細胞週期和細胞凋亡
- 胰島素訊號 Pathways
- Cancer Susceptibility (Verifying)


- Function pathway

- ATM 缺乏造成的可能反應
- 動脈硬化
- 膽固醇上升
- 心臟疾病
- 胰島素阻抗增加


- ATM and Cancer Susceptibility
- impact of ATM mutations on other cancer susceptibility is still controversial, as for breast cancer.

## Reference
- [UniProtKB-Q13315 (ATM_HUMAN)](https://www.uniprot.org/uniprot/Q13315)
- [Protein Structure PDB](https://www.rcsb.org/search?request=%7B%22query%22%3A%7B%22parameters%22%3A%7B%22attribute%22%3A%22rcsb_polymer_entity.pdbx_description%22%2C%22operator%22%3A%22contains_phrase%22%2C%22value%22%3A%22Serine-protein%20kinase%20ATM%22%7D%2C%22service%22%3A%22text%22%2C%22type%22%3A%22terminal%22%2C%22node_id%22%3A0%7D%2C%22return_type%22%3A%22entry%22%2C%22request_options%22%3A%7B%22pager%22%3A%7B%22start%22%3A0%2C%22rows%22%3A100%7D%2C%22scoring_strategy%22%3A%22combined%22%2C%22sort%22%3A%5B%7B%22sort_by%22%3A%22score%22%2C%22direction%22%3A%22desc%22%7D%5D%7D%2C%22request_info%22%3A%7B%22src%22%3A%22ui%22%2C%22query_id%22%3A%2206b3fc177ee7ea992aa74bae1013384c%22%7D%7D)
- [STITCH Interaction networks](http://stitch.embl.de/cgi/network.pl?taskId=RyHlmU0wY0dr)
- [Ataxia-Telangiectasia Mutated Modulation of Carbon Metabolism in Cancer](https://www.frontiersin.org/articles/10.3389/fonc.2017.00291/full)
- [ATM Pathway about DNA repair](https://www.frontiersin.org/files/Articles/319390/fonc-07-00291-HTML/image_m/fonc-07-00291-g001.jpg)
- [ATM Protein Kinase Signaling, Type 2 Diabetes and Cardiovascular Disease](https://www.researchgate.net/profile/Yolandi-Espach/publication/272511516_ATM_Protein_Kinase_Signaling_Type_2_Diabetes_and_Cardiovascular_Disease/links/54f03c460cf2495330e47ba0/ATM-Protein-Kinase-Signaling-Type-2-Diabetes-and-Cardiovascular-Disease.pdf)
- [ATM and P53 differentially regulate pancreatic beta cell survival in Ins1E cells](https://pubmed.ncbi.nlm.nih.gov/32810137/)
- [ATM Protein Kinase: Old and New Implications in
Neuronal Pathways and Brain Circuitry](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564642/)

## Question
- 非直接關聯的 pathway
- Inhibitor vs catalyst