9lo3 | pdb_00009lo3

Transition state analogue(GMPK in complex with GMP, ADP, Mg2+ and AlF4- at 277 K)

spinqualitylabelsall models 9lo3, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9lo3 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.75Å Ligands: 5GP, ADP, ALF, GOL, MG, PGE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KGUA_HUMAN Essential for recycling GMP and indirectly, cGMP. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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