2GVG

Crystal Structure of human NMPRTase and its complex with NMN

2GVG の概要

• エントリーDOI: 10.2210/pdb2gvg/pdb
• 関連するPDBエントリー: 2GVJ
• 分子名称: Nicotinamide phosphoribosyltransferase, PHOSPHATE ION, BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: nmprtase, visfatin, pbef, crystal, cancer, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (By similarity): P43490
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 336720.64

構造登録者

Khan, J.A.,Tao, X.,Tong, L. (登録日: 2006-05-02, 公開日: 2006-06-20, 最終更新日: 2024-02-14)

主引用文献

Khan, J.A.,Tao, X.,Tong, L.
Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents.
Nat.Struct.Mol.Biol., 13:582-588, 2006

PubMed Abstract: Nicotinamide phosphoribosyltransferase (NMPRTase) has a crucial role in the salvage pathway of NAD+ biosynthesis, and a potent inhibitor of NMPRTase, FK866, can reduce cellular NAD+ levels and induce apoptosis in tumors. We have determined the crystal structures at up to 2.1-A resolution of human and murine NMPRTase, alone and in complex with the reaction product nicotinamide mononucleotide or the inhibitor FK866. The structures suggest that Asp219 is a determinant of substrate specificity of NMPRTase, which is confirmed by our mutagenesis studies. FK866 is bound in a tunnel at the interface of the NMPRTase dimer, and mutations in this binding site can abolish the inhibition by FK866. Contrary to current knowledge, the structures show that FK866 should compete directly with the nicotinamide substrate. Our structural and biochemical studies provide a starting point for the development of new anticancer agents.

PubMed: 16783377
DOI: 10.1038/nsmb1105

実験手法

X-RAY DIFFRACTION (2.2 Å)