View source for 7pmz


==Crystal structure of Streptomyces coelicolor guaB (IMP dehydrogenase) bound to ATP and ppGpp at 2.0 A resolution==
<StructureSection load='7pmz' size='340' side='right'caption='[[7pmz]], [[Resolution|resolution]] 2.03&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7pmz]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_coelicolor_A3(2) Streptomyces coelicolor A3(2)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PMZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PMZ 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]] 2.03&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=G4P:GUANOSINE-5,3-TETRAPHOSPHATE'>G4P</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7pmz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pmz OCA], [https://pdbe.org/7pmz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pmz RCSB], [https://www.ebi.ac.uk/pdbsum/7pmz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pmz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9L0I7_STRCO Q9L0I7_STRCO] 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_01964]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
IMP dehydrogenase(IMPDH) is an essential enzyme that catalyzes the rate-limiting step in the guanine nucleotide pathway. In eukaryotic cells, GTP binding to the regulatory domain allosterically controls the activity of IMPDH by a mechanism that is fine-tuned by post-translational modifications and enzyme polymerization. Nonetheless, the mechanisms of regulation of IMPDH in bacterial cells remain unclear. Using biochemical, structural, and evolutionary analyses, we demonstrate that, in most bacterial phyla, (p)ppGpp compete with ATP to allosterically modulate IMPDH activity by binding to a, previously unrecognized, conserved high affinity pocket within the regulatory domain. This pocket was lost during the evolution of Proteobacteria, making their IMPDHs insensitive to these alarmones. Instead, most proteobacterial IMPDHs evolved to be directly modulated by the balance between ATP and GTP that compete for the same allosteric binding site. Altogether, we demonstrate that the activity of bacterial IMPDHs is allosterically modulated by a universally conserved nucleotide-controlled conformational switch that has divergently evolved to adapt to the specific particularities of each organism. These results reconcile the reported data on the crosstalk between (p)ppGpp signaling and the guanine nucleotide biosynthetic pathway and reinforce the essential role of IMPDH allosteric regulation on bacterial GTP homeostasis.

Diversity of mechanisms to control bacterial GTP homeostasis by the mutually exclusive binding of adenine and guanine nucleotides to IMP dehydrogenase.,Fernandez-Justel D, Marcos-Alcalde I, Abascal F, Vidana N, Gomez-Puertas P, Jimenez A, Revuelta JL, Buey RM Protein Sci. 2022 May;31(5):e4314. doi: 10.1002/pro.4314. PMID:35481629<ref>PMID:35481629</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7pmz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Buey RM]]
[[Category: Fernandez-Justel D]]
[[Category: Revuelta JL]]