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2gvj

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{{STRUCTURE_2gvj| PDB=2gvj | SCENE= }}
{{STRUCTURE_2gvj| PDB=2gvj | SCENE= }}
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'''Crystal Structure of Human NMPRTase in complex with FK866'''
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===Crystal Structure of Human NMPRTase in complex with FK866===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_16783377}}
==About this Structure==
==About this Structure==
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:35:24 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 01:46:39 2008''

Revision as of 22:46, 27 July 2008

Image:2gvj.png

Template:STRUCTURE 2gvj

Crystal Structure of Human NMPRTase in complex with FK866

Template:ABSTRACT PUBMED 16783377

About this Structure

2GVJ is a Single protein structure of sequence from Homo sapiens. 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

Page seeded by OCA on Mon Jul 28 01:46:39 2008

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