title: The structure of a eukaryotic nicotinic acid phosphoribosyltransferase reveals structural heterogeneity among type II PRTases.
abstract: Nicotinamide adenine dinucleotide (NAD) is an essential cofactor for cellular redox reactions and can act as an important substrate in numerous biological processes. As a result, nature has evolved multiple biosynthetic pathways to meet this high chemical demand. In Saccharomyces cerevisiae, the NAD salvage pathway relies on the activity of nicotinic acid phosphoribosyltransferase (NAPRTase), a member of the phosphoribosyltransferase (PRTase) superfamily. Here, we report the structure of a eukaryotic (yeast) NAPRTase at 1.75 A resolution (locus name: YOR209C, gene name: NPT1). The structure reveals a two-domain fold that resembles the architecture of quinolinic acid phosphoribosyltransferases (QAPRTases), but with completely different dispositions that provide evidence for structural heterogeneity among the Type II PRTases. The identification of a third domain in NAPRTases provides a structural basis and possible mechanism for the functional modulation of this family of enzymes by ATP.
authors.affiliation: The Joint Center for Structural Genomics, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Chappie
authors.forename: Jaume M
authors.initials: JM
authors.lastname: Cànaves
authors.forename: Gye Won
authors.initials: GW
authors.lastname: Han
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Rife
authors.forename: Qingping
authors.initials: Q
authors.lastname: Xu
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Stevens
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D009243:NAD / Q000096:biosynthesis; D010430:Pentosyltransferases / Q000737:chemistry*; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000201:enzymology*
chemical_list: D009243:NAD; D000255:Adenosine Triphosphate; D010430:Pentosyltransferases; C021864:nicotinate phosphoribosyltransferase