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Updated: Jul 9, 2026
10:17
A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
Published on: April 29, 2022
Structural genomics of protein phosphatases
Steven C Almo1, Jeffrey B Bonanno, J Michael Sauder
1Albert Einstein College of Medicine, Bronx, NY, USA. almo@aecom.yu.edu
Journal of Structural and Functional Genomics
|December 7, 2007
Summary
Researchers determined structures for 21 protein phosphatases from humans and pathogens, aiding drug discovery for diseases like malaria and type 1 diabetes.
Area of Science:
- Structural biology
- Genomics
- Biochemistry
Background:
- Protein phosphatases play crucial roles in cellular signaling and are implicated in various diseases.
- Understanding their structure is key to developing targeted therapies.
Purpose of the Study:
- To systematically determine the X-ray crystallographic structures of human protein phosphatases and those from biomedically relevant pathogens.
- To build a comprehensive structural database for drug discovery.
Main Methods:
- High-throughput X-ray crystallography was employed by the New York SGX Research Center for Structural Genomics (NYSGXRC).
- Structure determination focused on protein phosphatases from humans, mice, and pathogens like *Toxoplasma gondii*, *Trypanosoma brucei*, and *Anopheles gambiae*.
Main Results:
- Structures of 21 distinct protein phosphatases were determined: 14 human, 2 mouse, 2 *T. gondii*, 1 *T. brucei*, and 2 *A. gambiae*.
- These structures offer insights into transcriptional regulation, signaling pathways, neural development, and type 1 diabetes.
Conclusions:
- The determined structures contribute to an unprecedented database for structure-guided inhibitor discovery.
- This work supports the development of novel therapeutics targeting protein phosphatases across various diseases and organisms.
Related Concept Videos
02:54Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
02:54Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
01:02Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
01:02Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...