RESEARCH: CANCER
FOLDING PROJECT #18225 PROFILE

This project looks at Phosphoglycerate kinase (PGK), a protein important for how our cells use sugar for energy. Scientists are using computer simulations to understand how PGK works by seeing how its shape changes when it binds to different molecules.

Note: This TLDR is a simplication and may not be 100% accurate.

In this project we simulate the protein Phosphoglycerate kinase (PGK), a vital component in cell metabolism (specifically glycolysis, the processing of sugar into ATP for the cell).

PGK catalyzes the conversion of 1,3 bisphosphoglycerate to 3-phosphoglycerate generating one molecule of ATP in the process.

While the biochemical activity of PGK has been long understoon, how this process is achieved from a structural perspective is less well known. PGK deficiencies lead to hemolytic anemia and myopathy, over-expression has been linked to a variety of cancers, and PGK can metabolize a variety of different drugs.

We hope that simulations of PGK will lead to a better understanding of how PGK completes these essential catalytic activities. Our experimental collaborators have identified major shifts in PGK conformations as a function of the ligands (small molecules) bound to PGK.

In 18224, we simulate PGK in the unbound state.

In 18225, we simulate PGK with one of it's products (ADP) bound.

In 18226, we simulate PGK with one of it's substrates (ATP) bound.

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Phosphoglycerate kinase

An enzyme that catalyzes the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate in glycolysis.

Phosphoglycerate kinase (PGK) is a crucial enzyme involved in energy production within cells. It plays a key role in glycolysis, the process of breaking down sugar to generate ATP, the cell's primary energy currency. PGK catalyzes a specific step in glycolysis, converting 1,3-bisphosphoglycerate into 3-phosphoglycerate, while producing one molecule of ATP in the process. This enzyme is essential for cellular function and its dysfunction can lead to various health issues.

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Glycolysis

The metabolic pathway that converts glucose into pyruvate, producing ATP.

Glycolysis is the fundamental process by which cells break down glucose to generate energy. It's a series of chemical reactions occurring in the cytoplasm, converting one molecule of glucose into two molecules of pyruvate. This process yields a small amount of ATP, the cell's primary energy currency, and provides intermediates used in other metabolic pathways.

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ATP

Adenosine triphosphate

ATP (adenosine triphosphate) is the primary energy currency of cells. It's a high-energy molecule that stores and releases energy through the breaking and forming of phosphate bonds. ATP powers various cellular processes, including muscle contraction, protein synthesis, and nerve impulse transmission.

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Hemolytic anemia

A condition characterized by the premature destruction of red blood cells.

Hemolytic anemia is a medical condition where red blood cells are destroyed faster than the bone marrow can replace them. This leads to a shortage of healthy red blood cells, causing symptoms such as fatigue, weakness, pale skin, and shortness of breath. Various factors can contribute to hemolytic anemia, including genetic disorders, autoimmune diseases, infections, and certain medications.

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Myopathy

A disease or disorder of muscle tissue.

Myopathy refers to any condition affecting muscle function and structure. It can cause weakness, pain, stiffness, and difficulty with movement. Various factors can lead to myopathies, including genetic mutations, infections, autoimmune disorders, metabolic abnormalities, and certain medications.

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Cancer

A group of diseases characterized by uncontrolled cell growth and spread.

Cancer is a broad term encompassing various diseases marked by abnormal cell growth and proliferation. Cancer cells lose their normal regulatory mechanisms and invade surrounding tissues, potentially spreading to other parts of the body (metastasis). Numerous factors contribute to cancer development, including genetic predisposition, environmental exposures, lifestyle choices, and viral infections.