2gvl: Difference between revisions

Latest revision as of 08:05, 30 October 2024

Crystal Structure of Murine NMPRTase

Structural highlights

2gvl is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Ligands:	MSE
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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.

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rongvaux A, Shea RJ, Mulks MH, Gigot D, Urbain J, Leo O, Andris F. Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis. Eur J Immunol. 2002 Nov;32(11):3225-34. PMID:12555668 doi:<3225::AID-IMMU3225>3.0.CO;2-L https://dx.doi.org/10.1002/1521-4141(200211)32:11<3225::AID-IMMU3225>3.0.CO;2-L
↑ Revollo JR, Grimm AA, Imai S. The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem. 2004 Dec 3;279(49):50754-63. Epub 2004 Sep 20. PMID:15381699 doi:https://dx.doi.org/10.1074/jbc.M408388200
↑ Khan JA, Tao X, Tong L. Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents. Nat Struct Mol Biol. 2006 Jul;13(7):582-8. Epub 2006 Jun 18. PMID:16783377 doi:10.1038/nsmb1105

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Rongvaux A, Shea RJ, Mulks MH, Gigot D, Urbain J, Leo O, Andris F. Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis. Eur J Immunol. 2002 Nov;32(11):3225-34. PMID:12555668 doi:<3225::AID-IMMU3225>3.0.CO;2-L https://dx.doi.org/10.1002/1521-4141(200211)32:11<3225::AID-IMMU3225>3.0.CO;2-L

[2] Revollo JR, Grimm AA, Imai S. The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem. 2004 Dec 3;279(49):50754-63. Epub 2004 Sep 20. PMID:15381699 doi:https://dx.doi.org/10.1074/jbc.M408388200

[3] Khan JA, Tao X, Tong L. Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents. Nat Struct Mol Biol. 2006 Jul;13(7):582-8. Epub 2006 Jun 18. PMID:16783377 doi:10.1038/nsmb1105

[1]

[2]

[3]

@@ Line 3: / Line 3: @@
 <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/Lk3_transgenic_mice Lk3 transgenic mice]. 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>
+<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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nampt ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Nicotinamide_phosphoribosyltransferase Nicotinamide phosphoribosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.12 2.4.2.12] </span></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>
+[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]]
@@ Line 16: / Line 15: @@
    <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/initialview01.spt</scriptWhenUnchecked>
+     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>
    </jmolCheckbox>
@@ Line 38: / Line 37: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Mus musculus]]
-[[Category: Nicotinamide phosphoribosyltransferase]]
+[[Category: Khan JA]]
-[[Category: Khan, J A]]
+[[Category: Tao X]]
-[[Category: Tao, X]]
+[[Category: Tong L]]
-[[Category: Tong, L]]
-[[Category: Cancer]]
-[[Category: Fk866]]
-[[Category: Nmprtase]]
-[[Category: Pbef]]
-[[Category: Transferase]]
-[[Category: Visfatin]]

2gvl: Difference between revisions

Latest revision as of 08:05, 30 October 2024

Crystal Structure of Murine NMPRTase

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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