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2GVG

Crystal Structure of human NMPRTase and its complex with NMN

Summary for 2GVG
Entry DOI10.2210/pdb2gvg/pdb
Related2GVJ
DescriptorNicotinamide phosphoribosyltransferase, PHOSPHATE ION, BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE, ... (4 entities in total)
Functional Keywordsnmprtase, visfatin, pbef, crystal, cancer, transferase
Biological sourceHomo sapiens (human)
Cellular locationCytoplasm (By similarity): P43490
Total number of polymer chains6
Total formula weight336720.64
Authors
Khan, J.A.,Tao, X.,Tong, L. (deposition date: 2006-05-02, release date: 2006-06-20, Last modification date: 2024-02-14)
Primary citationKhan, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.2 Å)
Structure validation

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数据于2025-07-02公开中

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