View source for 6rpu


==Structure of the ternary complex of the IMPDH enzyme from Ashbya gossypii bound to the dinucleoside polyphosphate Ap5G and GDP==
<StructureSection load='6rpu' size='340' side='right'caption='[[6rpu]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6rpu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Eremothecium_gossypii_ATCC_10895 Eremothecium gossypii ATCC 10895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RPU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RPU 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]] 2.11&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=G5P:P1-(5-ADENOSYL)-P5-(5-GUANOSYL)+PENTAPHOSPHATE'>G5P</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</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=6rpu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rpu OCA], [https://pdbe.org/6rpu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rpu RCSB], [https://www.ebi.ac.uk/pdbsum/6rpu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rpu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q756Z6_ASHGO Q756Z6_ASHGO] 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.[HAMAP-Rule:MF_03156]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
IMP dehydrogenase (IMPDH) is an essential enzyme that catalyzes the rate-limiting step in the de novo guanine nucleotide biosynthetic pathway. Because of its involvement in the control of cell division and proliferation, IMPDH represents a therapeutic for managing several diseases, including microbial infections and cancer. IMPDH must be tightly regulated, but the molecular mechanisms responsible for its physiological regulation remain unknown. To this end, we recently reported an important role of adenine and guanine mononucleotides that bind to the regulatory Bateman domain to allosterically modulate the catalytic activity of eukaryotic IMPDHs. Here, we have used enzyme kinetics, X-ray crystallography, and small angle Xray scattering (SAXS) methodologies to demonstrate that adenine/guanine dinucleoside polyphosphates bind to the Bateman domain of IMPDH from the fungus Ashbya gossypii with submicromolar affinities. We found that these dinucleoside polyphosphates modulate the catalytic activity of IMPDHs in vitro by efficiently competing with the adenine/guanine mononucleotides for the allosteric sites. These results suggest that dinucleoside polyphosphates play important physiological roles in the allosteric regulation of IMPDHs by adding an additional mechanism for fine-tuning the activities of these enzymes. We propose that these findings may have important implications for the design of therapeutic strategies to inhibit IMPDHs.

The Bateman domain of IMP dehydrogenase is a binding target for dinucleoside polyphosphates.,Fernandez-Justel D, Pelaez R, Revuelta JL, Buey RM J Biol Chem. 2019 Aug 15. pii: AC119.010055. doi: 10.1074/jbc.AC119.010055. PMID:31416831<ref>PMID:31416831</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rpu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Inosine monophosphate dehydrogenase 3D structures|Inosine monophosphate dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Eremothecium gossypii ATCC 10895]]
[[Category: Large Structures]]
[[Category: Buey RM]]
[[Category: Fernandez-Justel D]]
[[Category: Revuelta JL]]