2gvg

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spinqualitylabelsall models 2gvg, resolution 2.2Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of human NMPRTase and its complex with NMN

Overview

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.

About this Structure

2GVG is a Single protein structure of sequence from Homo sapiens with PO4 and NMN as ligands. Active as Nicotinamide phosphoribosyltransferase, with EC number 2.4.2.12 Full crystallographic information is available from OCA.

Reference

Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents., Khan JA, Tao X, Tong L, Nat Struct Mol Biol. 2006 Jul;13(7):582-8. Epub 2006 Jun 18. PMID:16783377

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