4CYY

The structure of vanin-1: defining the link between metabolic disease, oxidative stress and inflammation

Summary for 4CYY

• Entry DOI: 10.2210/pdb4cyy/pdb
• Related: 4CYF 4CYG 4CYU
• Descriptor: PANTETHEINASE, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: hydrolase, inflammation, oxidative stress, metabolic disease, coa biosynthesis
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 57634.45

Authors

Boersma, Y.L.,Newman, J.,Adams, T.E.,Sparrow, L.,Cowieson, N.,Lucent, D.,Krippner, G.,Bozaoglu, K.,Peat, T.S. (deposition date: 2014-04-16, release date: 2014-12-10, Last modification date: 2023-12-20)

Primary citation

Boersma, Y.L.,Newman, J.,Adams, T.E.,Cowieson, N.,Krippner, G.,Bozaoglu, K.,Peat, T.S.
The Structure of Vanin-1: A Key Enzyme Linking Metabolic Disease and Inflammation
Acta Crystallogr.,Sect.D, 70:3320-, 2014

PubMed Abstract: 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 B5) 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 Å 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.

PubMed: 25478849
DOI: 10.1107/S1399004714022767

Experimental method

X-RAY DIFFRACTION (2.89 Å)