title: The structure of vanin 1: a key enzyme linking metabolic disease and inflammation.
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.
authors.affiliation: Department of Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Ykelien L
authors.initials: YL
authors.lastname: Boersma
authors.affiliation: CSIRO Biosciences Program, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Janet
authors.initials: J
authors.lastname: Newman
authors.affiliation: CSIRO Biosciences Program, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Adams
authors.affiliation: Australian Synchrotron, 800 Blackburn Road, Clayton, VIC 3168, Australia.
authors.forename: Nathan
authors.initials: N
authors.lastname: Cowieson
authors.affiliation: Baker IDI, 75 Commercial Road, Melbourne, VIC 3004, Australia.
authors.forename: Guy
authors.initials: G
authors.lastname: Krippner
authors.affiliation: Baker IDI, 75 Commercial Road, Melbourne, VIC 3004, Australia.
authors.forename: Kiymet
authors.initials: K
authors.lastname: Bozaoglu
authors.affiliation: CSIRO Biosciences Program, 343 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Peat
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D018360:Crystallography, X-Ray; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
chemical_list: D058851:GPI-Linked Proteins; D000581:Amidohydrolases; C022314:pantetheinase
keywords: CoA biosynthesis; colitis; inflammation; metabolic disease; vanin 1