1lvg

Crystal structure of mouse guanylate kinase in complex with GMP and ADP

spinqualitylabelsall models 1lvg, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1lvg is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: 5GP, ADP, K Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KGUA_MOUSE Essential for recycling GMP and indirectly, cGMP. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Guanylate kinase (GMPK) is a nucleoside monophosphate kinase that catalyzes the reversible phosphoryl transfer from ATP to GMP to yield ADP and GDP. In addition to phosphorylating GMP, antiviral prodrugs such as acyclovir, ganciclovir, and carbovir and anticancer prodrugs such as the thiopurines are dependent on GMPK for their activation. Hence, structural information on mammalian GMPK could play a role in the design of improved antiviral and antineoplastic agents. Here we present the structure of the mouse enzyme in an abortive complex with the nucleotides ADP and GMP, refined at 2.1 A resolution with a final crystallographic R factor of 0.19 (R(free) = 0.23). Guanylate kinase is a member of the nucleoside monophosphate (NMP) kinase family, a family of enzymes that despite having a low primary structure identity share a similar fold, which consists of three structurally distinct regions termed the CORE, LID, and NMP-binding regions. Previous studies on the yeast enzyme have shown that these parts move as rigid bodies upon substrate binding. It has been proposed that consecutive binding of substrates leads to "closing" of the active site bringing the NMP-binding and LID regions closer to each other and to the CORE region. Our structure, which is the first of any guanylate kinase with both substrates bound, supports this hypothesis. It also reveals the binding site of ATP and implicates arginines 44, 137, and 148 (in addition to the invariant P-loop lysine) as candidates for catalyzing the chemical step of the phosphoryl transfer. Structural characterization of the closed conformation of mouse guanylate kinase.,Sekulic N, Shuvalova L, Spangenberg O, Konrad M, Lavie A J Biol Chem. 2002 Aug 16;277(33):30236-43. Epub 2002 May 29. PMID:12036965 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Guanylate kinase 3D structures

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