View source for 9lo3


==Transition state analogue(GMPK in complex with GMP, ADP, Mg2+ and AlF4- at 277 K)==
<StructureSection load='9lo3' size='340' side='right'caption='[[9lo3]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9lo3]] is a 1 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=9LO3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9LO3 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]] 1.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5GP:GUANOSINE-5-MONOPHOSPHATE'>5GP</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ALF:TETRAFLUOROALUMINATE+ION'>ALF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=9lo3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9lo3 OCA], [https://pdbe.org/9lo3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9lo3 RCSB], [https://www.ebi.ac.uk/pdbsum/9lo3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9lo3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KGUA_HUMAN KGUA_HUMAN] Essential for recycling GMP and indirectly, cGMP.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human guanylate kinase (GMPK) as the sole enzyme for GDP biosynthesis plays pivotal roles in antiviral prodrug activation and tumorigenesis. Despite its biological significance, the catalytic mechanism remains poorly understood. Here, we resolve crystal structures of GMPK in free and GMP-bound form, revealing the interdomain motions of GMPBD and LID relative to the CORE domain. Biochemical assays demonstrate potassium's dual functionality in substrate recognition and phosphoryl transfer catalysis. Structural analyses uncover intradomain conformational motion within the LID domain and essential interactions for ADP/ATP binding. Notably, the cooperative ATPgammaS binding potentiated by prior GMP binding are structurally elucidated. Three key complexes, pre-reaction state (GMP/ATPgammaS), transition state (AlF(4)(-) mimic), and post-reaction state (GDP/ADP), collectively delineate the reversible catalytic pathway. This comprehensive structural characterization of GMPK's dynamic landscape establishes a foundation for developing conformation-specific inhibitors through structure-guided drug design.

Comprehensive profiling of the catalytic conformations of human Guanylate kinase.,Wang L, Li Z, Xuan Y, Qin J, Li S, Zhong F, Song Y, Yang K, Lv M, Li F, Jiahai Z, Pan Y, Guang S, Zhao Y, Shi Y, Liu X, Du Y, Gao J, Ruan K Nat Commun. 2025 Jul 25;16(1):6859. doi: 10.1038/s41467-025-61732-y. PMID:40715061<ref>PMID:40715061</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9lo3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ruan K]]
[[Category: Wang L]]