2gvl: Difference between revisions

Revision as of 05:35, 4 May 2008

Crystal Structure of Murine NMPRTase

OverviewOverview

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 StructureAbout this Structure

2GVL is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

ReferenceReference

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 Sun May 4 05:35:34 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:2gvl.gif|left|200px]]
- {{Structure
+<!--
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+The line below this paragraph, containing "STRUCTURE_2gvl", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= Nampt ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])
+-->
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-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gvl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gvl OCA], [http://www.ebi.ac.uk/pdbsum/2gvl PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2gvl RCSB]</span>
-}}
 '''Crystal Structure of Murine NMPRTase'''
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 [[Category: Tao, X.]]
 [[Category: Tong , L.]]
-[[Category: cancer]]
+[[Category: Cancer]]
-[[Category: fk866]]
+[[Category: Fk866]]
-[[Category: nmprtase]]
+[[Category: Nmprtase]]
-[[Category: pbef]]
+[[Category: Pbef]]
-[[Category: visfatin]]
+[[Category: Visfatin]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 05:35:34 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:22:13 2008''