The structure of vanin 1: a key enzyme linking metabolic disease and inflammation

作者：Boersma Ykelien L; Newman Janet; Adams Timothy E; Cowieson Nathan; Krippner Guy; Bozaoglu Kiymet; Peat Thomas S^*

来源：Acta Crystallographica Section D-Structural Biology, 2014, 70(12): 3320-3329.

DOI：10.1107/S1399004714022767

Although part of the coenzyme A pathway, vanin 1 (also known as pantetheinase) sits on the cell surface of many cell types as an ectoenzyme, catalyzing the breakdown of pantetheine to pantothenic acid (vitamin B-5) and cysteamine, a strong reducing agent. Vanin 1 was initially discovered as a protein involved in the homing of leukocytes to the thymus. Numerous studies have shown that vanin 1 is involved in inflammation, and more recent studies have shown a key role in metabolic disease. Here, the X-ray crystal structure of human vanin 1 at 2.25 angstrom resolution is presented, which is the first reported structure from the vanin family, as well as a crystal structure of vanin 1 bound to a specific inhibitor. These structures illuminate how vanin 1 can mediate its biological roles by way of both enzymatic activity and protein-protein interactions. Furthermore, it sheds light on how the enzymatic activity is regulated by a novel allosteric mechanism at a domain interface.

• 出版日期2014-12