2cxu

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(New page: 200px<br /><applet load="2cxu" size="450" color="white" frame="true" align="right" spinBox="true" caption="2cxu, resolution 1.65&Aring;" /> '''Crystal structure of...)
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[[Image:2cxu.gif|left|200px]]<br /><applet load="2cxu" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2cxu, resolution 1.65&Aring;" />
 
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'''Crystal structure of mouse AMF / M6P complex'''<br />
 
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==Overview==
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==Crystal structure of mouse AMF / M6P complex==
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Autocrine motility factor (AMF), a tumor-secreted cytokine, stimulates, cell migration in vitro and metastasis in vivo. AMF is identical to the, extracellular cytokines neuroleukin and maturation factor and, interestingly, to the intracellular enzyme phosphoglucose isomerase. The, cytokine activity of AMF is inhibited by carbohydrate phosphate compounds, as they compete for AMF binding with the carbohydrate moiety of the AMF, receptor (AMFR), which is a glycosylated seven transmembrane helix, protein. Here, we report the first comprehensive high-resolution crystal, structure analyses of the inhibitor-free form and the eight types of, inhibitor (phosphate, erythrose 4-phosphate (E4P), arabinose 5-phosphate, (A5P), sorbitol 6-phosphate (S6P), 6-phosphogluconic acid (6PGA), fructose, 6-phosphate (F6P), glucose 6-phosphate (G6P), or mannose 6-phosphate, (M6P)) complexes of mouse AMF (mAMF). We assayed the inhibitory activities, of these inhibitors against the cytokine activity of mAMF. The inhibitory, activities of the six-carbon sugars (G6P, F6P, M6P, and 6PGA) were found, to be significantly higher than those of the four or five-carbon sugars, (E4P or A5P). The inhibitory activities clearly depend on the length of, the inhibitor molecules. A structural comparison revealed that a, water-mediated hydrogen bond between one end of the inhibitor and a rigid, portion of the protein surface in the shorter-chain inhibitor (E4P), complex is replaced by a direct hydrogen bond in the longer-chain, inhibitor (6PGA) complex. Thus, to obtain a new compound with higher, inhibitory activities against AMF, water molecules at the inhibitor, binding site of AMF should be replaced by a functional group of inhibitors, in order to introduce direct interactions with the protein surface. The, present structure-activity relationship studies will be valuable not only, for designing more effective AMF inhibitors but also for studying general, protein-inhibitor interactions.
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<StructureSection load='2cxu' size='340' side='right'caption='[[2cxu]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2cxu]] 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=2CXU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CXU FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2cxu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cxu OCA], [https://pdbe.org/2cxu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cxu RCSB], [https://www.ebi.ac.uk/pdbsum/2cxu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cxu ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/G6PI_MOUSE G6PI_MOUSE] Besides it's role as a glycolytic enzyme, mammalian GPI can function as a tumor-secreted cytokine and an angiogenic factor (AMF) that stimulates endothelial cell motility. GPI is also a neurotrophic factor (Neuroleukin) for spinal and sensory neurons.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cx/2cxu_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2cxu ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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2CXU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with PO4 and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glucose-6-phosphate_isomerase Glucose-6-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.9 5.3.1.9] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CXU OCA].
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*[[Phosphoglucose isomerase 3D structures|Phosphoglucose isomerase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Crystal structures of mouse autocrine motility factor in complex with carbohydrate phosphate inhibitors provide insight into structure-activity relationship of the inhibitors., Tanaka N, Haga A, Naba N, Shiraiwa K, Kusakabe Y, Hashimoto K, Funasaka T, Nagase H, Raz A, Nakamura KT, J Mol Biol. 2006 Feb 17;356(2):312-24. Epub 2005 Dec 9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16375918 16375918]
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[[Category: Large Structures]]
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[[Category: Glucose-6-phosphate isomerase]]
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[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Single protein]]
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[[Category: Funasaka T]]
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[[Category: Funasaka, T.]]
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[[Category: Haga A]]
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[[Category: Haga, A.]]
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[[Category: Hashimoto K]]
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[[Category: Hashimoto, K.]]
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[[Category: Kusakabe Y]]
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[[Category: Kusakabe, Y.]]
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[[Category: Naba N]]
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[[Category: Naba, N.]]
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[[Category: Nagase H]]
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[[Category: Nagase, H.]]
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[[Category: Nakamura KT]]
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[[Category: Nakamura, K.T.]]
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[[Category: Raz A]]
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[[Category: Raz, A.]]
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[[Category: Shiraiwa K]]
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[[Category: Shiraiwa, K.]]
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[[Category: Tanaka N]]
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[[Category: Tanaka, N.]]
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[[Category: GOL]]
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[[Category: PO4]]
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[[Category: isomerase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 09:19:59 2007''
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Current revision

Crystal structure of mouse AMF / M6P complex

PDB ID 2cxu

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