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| | <StructureSection load='6i0o' size='340' side='right'caption='[[6i0o]], [[Resolution|resolution]] 2.62Å' scene=''> | | <StructureSection load='6i0o' size='340' side='right'caption='[[6i0o]], [[Resolution|resolution]] 2.62Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6i0o]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I0O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I0O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6i0o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I0O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I0O FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.623Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6i0m|6i0m]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IMPDH2, IMPD2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6i0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i0o OCA], [https://pdbe.org/6i0o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i0o RCSB], [https://www.ebi.ac.uk/pdbsum/6i0o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i0o ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/IMP_dehydrogenase IMP dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.205 1.1.1.205] </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=6i0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i0o OCA], [http://pdbe.org/6i0o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i0o RCSB], [http://www.ebi.ac.uk/pdbsum/6i0o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i0o ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IMDH2_HUMAN IMDH2_HUMAN]] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.[HAMAP-Rule:MF_03156] | + | [https://www.uniprot.org/uniprot/IMDH2_HUMAN IMDH2_HUMAN] Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.[HAMAP-Rule:MF_03156] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6i0o" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6i0o" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Inosine monophosphate dehydrogenase 3D structures|Inosine monophosphate dehydrogenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: IMP dehydrogenase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Buey, R M]] | + | [[Category: Buey RM]] |
| - | [[Category: Fernandez-Justel, D]] | + | [[Category: Fernandez-Justel D]] |
| - | [[Category: Revuelta, J L]] | + | [[Category: Revuelta JL]] |
| - | [[Category: Biosynthetic protein]]
| + | |
| - | [[Category: De novo guanine nucleotide biosynthesis]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
IMDH2_HUMAN Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.[HAMAP-Rule:MF_03156]
Publication Abstract from PubMed
IMP dehydrogenase (IMPDH) catalyzes the rate-limiting step in the de novo GTP biosynthetic pathway and plays essential roles in cell proliferation. As a clinical target, IMPDH has been studied for decades but it has only been within the last years that we are starting to understand the complexity of the mechanisms of its physiological regulation. Here, we report structural and functional insights into how adenine and guanine nucleotides control a conformational switch that modulates the assembly of the two human IMPDH enzymes into cytoophidia and allosterically regulates their catalytic activity. In vitro reconstituted micron-length cytoophidia-like structures show catalytic activity comparable to unassembled IMPDH but, in turn, are more resistant to GTP/GDP allosteric inhibition. Therefore, IMPDH cytoophidia formation facilitates the accumulation of high levels of guanine nucleotides when the cell requires it. Finally, we demonstrate that most of the IMPDH retinopathy-associated mutations abrogate GTP/GDP-induced allosteric inhibition and alter cytoophidia dynamics.
A Nucleotide-Dependent Conformational Switch Controls the Polymerization of Human IMP Dehydrogenases to Modulate their Catalytic Activity.,Fernandez-Justel D, Nunez R, Martin-Benito J, Jimeno D, Gonzalez-Lopez A, Soriano EM, Revuelta JL, Buey RM J Mol Biol. 2019 Jan 18. pii: S0022-2836(19)30029-4. doi:, 10.1016/j.jmb.2019.01.020. PMID:30664871[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fernandez-Justel D, Nunez R, Martin-Benito J, Jimeno D, Gonzalez-Lopez A, Soriano EM, Revuelta JL, Buey RM. A Nucleotide-Dependent Conformational Switch Controls the Polymerization of Human IMP Dehydrogenases to Modulate their Catalytic Activity. J Mol Biol. 2019 Jan 18. pii: S0022-2836(19)30029-4. doi:, 10.1016/j.jmb.2019.01.020. PMID:30664871 doi:http://dx.doi.org/10.1016/j.jmb.2019.01.020
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