CHST1

CHST1

The protein structure of CHST1.

CHST1 (Carbohydrate Sulfotransferase 1) is an enzyme that plays a crucial role in the sulfation of carbohydrates. It is encoded by the CHST1 gene, which is located on chromosome 11 in humans. CHST1 is primarily expressed in the cartilage and is involved in the biosynthesis of chondroitin sulfate, a major component of cartilage extracellular matrix.

Structure

The CHST1 protein consists of 389 amino acids and has a molecular weight of approximately 44 kDa. It belongs to the sulfotransferase family and contains a conserved sulfotransferase domain. The protein structure of CHST1 has been determined through X-ray crystallography, revealing its active site and substrate-binding region.

Function

CHST1 catalyzes the transfer of sulfate groups from the universal sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to specific positions on the carbohydrate chains of proteoglycans. Specifically, it sulfates the C4 hydroxyl group of N-acetylgalactosamine (GalNAc) residues in chondroitin sulfate. This sulfation process is essential for the proper formation and function of cartilage.

Role in Cartilage Development

Chondroitin sulfate is a critical component of cartilage, providing structural integrity and elasticity to the tissue. The sulfation of chondroitin sulfate by CHST1 is crucial for its interaction with other molecules, such as growth factors and extracellular matrix proteins. These interactions are essential for cartilage development, maintenance, and repair.

Mutations in the CHST1 gene have been associated with skeletal dysplasias, a group of genetic disorders characterized by abnormal bone and cartilage development. These mutations can lead to a decrease in CHST1 activity, resulting in impaired sulfation of chondroitin sulfate and subsequent cartilage defects.

Clinical Significance

Alterations in CHST1 expression and activity have been implicated in various pathological conditions. For example, increased CHST1 expression has been observed in certain types of cancer, including breast and lung cancer. This upregulation of CHST1 is thought to contribute to tumor progression and metastasis by promoting the remodeling of the extracellular matrix.

Furthermore, CHST1 has been identified as a potential therapeutic target for the treatment of osteoarthritis. Inhibition of CHST1 activity could potentially reduce the excessive sulfation of chondroitin sulfate in osteoarthritic cartilage, thereby alleviating cartilage degradation and joint pain.

See Also

• Proteoglycan
• Chondroitin Sulfate
• Cartilage
• Sulfotransferase
• Osteoarthritis