5ayz

CRYSTAL STRUCTURE OF HUMAN QUINOLINATE PHOSPHORIBOSYLTRANSFERASE IN COMPLEX WITH THE PRODUCT NICOTINATE MONONUCLEOTIDE

spinqualitylabelsall models 5ayz, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ayz is a 12 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 4r3y. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NCN Related: 4r3x Gene: HEL-S-90n, QPRT (HUMAN) Activity: Nicotinate-nucleotide diphosphorylase (carboxylating), with EC number 2.4.2.19 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [V9HWJ5_HUMAN] Involved in the catabolism of quinolinic acid (QA).[PIRNR:PIRNR006250] Publication Abstract from PubMed Quinolinate phosphoribosyltransferase (QPRT) catalyses the production of nicotinic acid mononucleotide, a precursor of de novo biosynthesis of the ubiquitous coenzyme nicotinamide adenine dinucleotide. QPRT is also essential for maintaining the homeostasis of quinolinic acid in the brain, a possible neurotoxin causing various neurodegenerative diseases. Although QPRT has been extensively analysed, the molecular basis of the reaction catalysed by human QPRT remains unclear. Here, we present the crystal structures of hexameric human QPRT in the apo form and its complexes with reactant or product. We found that the interaction between dimeric subunits was dramatically altered during the reaction process by conformational changes of two flexible loops in the active site at the dimer-dimer interface. In addition, the N-terminal short helix alpha1 was identified as a critical hexamer stabilizer. The structural features, size distribution, heat aggregation and ITC studies of the full-length enzyme and the enzyme lacking helix alpha1 strongly suggest that human QPRT acts as a hexamer for cooperative reactant binding via three dimeric subunits and maintaining stability. Based on our comparison of human QPRT structures in the apo and complex forms, we propose a drug design strategy targeting malignant glioma. Structural Insights into the Quaternary Catalytic Mechanism of Hexameric Human Quinolinate Phosphoribosyltransferase, a Key Enzyme in de novo NAD Biosynthesis.,Youn HS, Gyun Kim T, Kim MK, Bu Kang G, Youn Kang J, Lee JG, Yop An J, Ryoung Park K, Lee Y, Jun Im Y, Hyuck Lee J, Hyun Eom S Sci Rep. 2016 Jan 25;6:19681. doi: 10.1038/srep19681. PMID:26805589 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoribosyltransferase 3D structures

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