Endothelin-converting enzyme 1

Endothelin-converting enzyme 1

Endothelin-converting enzyme 1 structure

Endothelin-converting enzyme 1 (ECE-1) is a membrane-bound metalloprotease enzyme that plays a crucial role in the production and regulation of endothelins. It is encoded by the ECE1 gene located on chromosome 1 in humans. ECE-1 is primarily expressed in endothelial cells, where it cleaves inactive big endothelins into their active forms, leading to vasoconstriction and other physiological effects.

Structure

The structure of ECE-1 consists of a large extracellular catalytic domain, a transmembrane domain, and a short cytoplasmic tail. The catalytic domain contains a zinc-binding motif and a conserved HEXXHXXGXXH motif, which are characteristic of metalloproteases. The transmembrane domain anchors the enzyme to the cell membrane, allowing it to interact with its substrates and other cellular components.

Function

ECE-1 is primarily responsible for the conversion of big endothelins, which are inactive precursors, into their active forms, endothelin-1, endothelin-2, and endothelin-3. This conversion occurs through the cleavage of the precursor peptides at specific sites, resulting in the release of the biologically active endothelins. Endothelins are potent vasoconstrictors and also have various effects on cell growth, inflammation, and tissue remodeling.

Role in Physiology

ECE-1 plays a critical role in maintaining vascular tone and blood pressure regulation. By converting big endothelins into their active forms, ECE-1 contributes to vasoconstriction, which helps regulate blood flow and blood pressure. Dysregulation of ECE-1 activity has been implicated in various cardiovascular diseases, including hypertension, atherosclerosis, and heart failure.

Clinical Significance

Due to its involvement in cardiovascular diseases, ECE-1 has emerged as a potential therapeutic target. Inhibitors of ECE-1 have been developed and tested for their ability to modulate endothelin levels and improve cardiovascular function. These inhibitors have shown promise in preclinical studies and are being investigated for their potential use in the treatment of hypertension and other cardiovascular disorders.

See Also

• Endothelin
• Metalloprotease
• Cardiovascular diseases
• Hypertension
• Atherosclerosis
• Heart failure