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| | <StructureSection load='2cxu' size='340' side='right'caption='[[2cxu]], [[Resolution|resolution]] 1.65Å' scene=''> | | <StructureSection load='2cxu' size='340' side='right'caption='[[2cxu]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2cxu]] is a 2 chain structure with sequence from [http://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=2CXU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CXU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2cxu]] 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=2CXU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CXU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><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> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2cvp|2cvp]], [[2cxn|2cxn]], [[2cxo|2cxo]], [[2cxp|2cxp]], [[2cxq|2cxq]], [[2cxr|2cxr]], [[2cxs|2cxs]], [[2cxt|2cxt]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2cvp|2cvp]], [[2cxn|2cxn]], [[2cxo|2cxo]], [[2cxp|2cxp]], [[2cxq|2cxq]], [[2cxr|2cxr]], [[2cxs|2cxs]], [[2cxt|2cxt]]</div></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glucose-6-phosphate_isomerase Glucose-6-phosphate isomerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.9 5.3.1.9] </span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2cxu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cxu OCA], [http://pdbe.org/2cxu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2cxu RCSB], [http://www.ebi.ac.uk/pdbsum/2cxu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2cxu ProSAT]</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=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> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [[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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Phosphoglucoisomerase|Phosphoglucoisomerase]] | |
| | *[[Phosphoglucose isomerase 3D structures|Phosphoglucose isomerase 3D structures]] | | *[[Phosphoglucose isomerase 3D structures|Phosphoglucose isomerase 3D structures]] |
| | == References == | | == References == |
| Structural highlights
Function
[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.
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
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.
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:16375918[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tanaka N, Haga A, Naba N, Shiraiwa K, Kusakabe Y, Hashimoto K, Funasaka T, Nagase H, Raz A, Nakamura KT. Crystal structures of mouse autocrine motility factor in complex with carbohydrate phosphate inhibitors provide insight into structure-activity relationship of the inhibitors. J Mol Biol. 2006 Feb 17;356(2):312-24. Epub 2005 Dec 9. PMID:16375918 doi:http://dx.doi.org/10.1016/j.jmb.2005.11.076
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