2gvl: Difference between revisions

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-[[Image:2gvl.gif|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_2gvl", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
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-{{STRUCTURE_2gvl|  PDB=2gvl  |  SCENE=  }}
-'''Crystal Structure of Murine NMPRTase'''
+==Crystal Structure of Murine NMPRTase==
+<StructureSection load='2gvl' size='340' side='right'caption='[[2gvl]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2gvl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GVL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GVL FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2gvl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gvl OCA], [https://pdbe.org/2gvl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gvl RCSB], [https://www.ebi.ac.uk/pdbsum/2gvl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gvl ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/NAMPT_MOUSE NAMPT_MOUSE] Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway.<ref>PMID:12555668</ref> <ref>PMID:15381699</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gv/2gvl_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2gvl ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-==Overview==
+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<ref>PMID:16783377</ref>
-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==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-GVL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GVL OCA].
+</div>
+<div class="pdbe-citations 2gvl" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-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:[http://www.ncbi.nlm.nih.gov/pubmed/16783377 16783377]
+*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Nicotinamide phosphoribosyltransferase]]
+[[Category: Khan JA]]
-[[Category: Single protein]]
+[[Category: Tao X]]
-[[Category: Khan, J A.]]
+[[Category: Tong L]]
-[[Category: Tao, X.]]
-[[Category: Tong , L.]]
-[[Category: Cancer]]
-[[Category: Fk866]]
-[[Category: Nmprtase]]
-[[Category: Pbef]]
-[[Category: Visfatin]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 05:35:34 2008''