2gvl
From Proteopedia
(New page: 200px<br /><applet load="2gvl" size="450" color="white" frame="true" align="right" spinBox="true" caption="2gvl, resolution 2.10Å" /> '''Crystal Structure of...) |
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| - | [[Image:2gvl.gif|left|200px]]<br /><applet load="2gvl" size=" | + | [[Image:2gvl.gif|left|200px]]<br /><applet load="2gvl" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2gvl, resolution 2.10Å" /> | caption="2gvl, resolution 2.10Å" /> | ||
'''Crystal Structure of Murine NMPRTase'''<br /> | '''Crystal Structure of Murine NMPRTase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Nicotinamide phosphoribosyltransferase (NMPRTase) has a crucial role in | + | 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== | ==About this Structure== | ||
| - | 2GVL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Nicotinamide_phosphoribosyltransferase Nicotinamide phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.12 2.4.2.12] Full crystallographic information is available from [http:// | + | 2GVL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Nicotinamide_phosphoribosyltransferase Nicotinamide phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.12 2.4.2.12] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GVL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Nicotinamide phosphoribosyltransferase]] | [[Category: Nicotinamide phosphoribosyltransferase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Khan, J | + | [[Category: Khan, J A.]] |
[[Category: Tao, X.]] | [[Category: Tao, X.]] | ||
[[Category: Tong , L.]] | [[Category: Tong , L.]] | ||
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[[Category: visfatin]] | [[Category: visfatin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:35:51 2008'' |
Revision as of 15:35, 21 February 2008
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Crystal Structure of Murine NMPRTase
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
2GVL is a Single protein structure of sequence from Mus musculus. 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
Page seeded by OCA on Thu Feb 21 17:35:51 2008
