Disease relevance of GUK1

• Using inducible expression systems, guanylate kinase was produced in large amounts both in S. cerevisiae and in Escherichia coli [1].

High impact information on GUK1

• A major palmitoylated membrane protein of human erythrocytes shows homology to yeast guanylate kinase and to the product of a Drosophila tumor suppressor gene [2].
• Sequencing of a near full-length cDNA predicts a protein containing a domain homologous to yeast guanylate kinase and a region homologous to SH3, a putative regulatory motif in nonreceptor protein tyrosine kinases and other signal transduction proteins [3].
• Is the erythrocyte protein p55 a membrane-bound guanylate kinase [4]?
• The GK domain of MAGUKs, which shares high similarity in amino acid sequence with yeast guanylate kinase (yGMPK), is the least characterized MAGUK domain both in structure and function [5].
• Only this first step of GDP synthesis pathway is regulated, since the latter steps, encoded by the GUA1 and GUK1 genes, are guanine-insensitive [6].

Biological context of GUK1

• Using oligonucleotides based on amino acid sequence information of the yeast enzyme, the Saccharomyces cerevisiae gene, GUK1, was isolated and characterized [1].
• Insertional mutagenesis of the GUK1 locus caused recessive lethality, indicating that this enzyme is necessary for vegetative cell growth [1].
• Cloning and expression of the essential gene for guanylate kinase from yeast [1].
• The structure of the recombinant GK.GMP complex superimposes very well with that of the native GK.GMP complex, indicating that N-terminal acetylation does not have significant impact on the three-dimensional structure of GK [7].
• Second, overexpression of HPT1 allows suppression of the deregulated phenotype of the guk1 mutants [8].

Anatomical context of GUK1

• Overexpression of MSN17 increased the GDP-mannose level in a wild-type strain by about threefold, and guk1 decreased the GDP-mannose level to one-fourth, suggesting a close relationship between GTP metabolism and mannose outer chain elongation; the link is presumably provided by the process of GDP-mannose transport in the Golgi membranes [9].
• We confirmed the ability of GK to substitute for complete cytosol by reconstitution of glycopeptide export from rat liver microsomes using highly purified recombinant GK from Saccharomyces cerevisiae [10].
• By a yeast two-hybrid approach, we identified an interaction between the GUK domain of CASK and the C2B domain of rabphilin3a, a presynaptic protein involved in synaptic vesicle exocytosis [11].
• MAGUK with inverted domain structure-1 (MAGI-1) is a membrane-associated protein with one guanylate kinase, six PSD-95/Dlg-A/ZO-1 (PDZ), and two WW domains and is localized at tight junctions in epithelial cells [12].

Associations of GUK1 with chemical compounds

• Structural and functional roles of tyrosine 78 of yeast guanylate kinase [13].
• Guanylate kinase catalyzes the reversible transfer of the terminal phosphoryl group of ATP to the acceptor molecule GMP [1].
• The hydroxyl group of Tyr-78 of yeast guanylate kinase (GK) is hydrogen-bonded to the phosphate of the bound GMP as revealed by x-ray crystallography [13].
• Guanylate kinase is structurally related to adenylate kinases and G-proteins with respect to its central beta-sheet with connecting helices and the giant anion hole that binds nucleoside triphosphates [14].
• The bra3 mutants have a low GMP kinase activity, excrete purines in the medium, and show vegetative growth defects and resistance to purine base analogs [8].

Other interactions of GUK1

• Binding of nucleotides to guanylate kinase, p21(ras), and nucleoside-diphosphate kinase studied by nano-electrospray mass spectrometry [15].

Analytical, diagnostic and therapeutic context of GUK1

• This paper describes a large-scale purification of guanylate kinase (ATP + GMP in equilibrium ADP + GDP) from Saccharomyces cerevisiae, the crystallization of the enzyme and preliminary X-ray investigations [16].
• 1. Guanylate kinase was purified in five steps to homogeneity: crude extract, ion-exchange chromatography, affinity chromatography and gel filtration twice [16].
• NMR titration and equilibrium dialysis showed that both substrates and products could bind to free guanylate kinase [17].
• The protein was identified by mass spectrometric sequence analysis as guanylate kinase (GK), a housekeeping enzyme critical in the regulation of cellular GTP levels [10].
• We verified interaction of Act with murine and human SNAP23, galectin-3, and GUK-1 by sandwich Western blot analysis [18].

References