Publications

• Purification and properties of guanylate kinase from Escherichia coli.

  Oeschger M.P., Bessman M.J.

  J Biol Chem 241:5452-5460(1966) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Solution structure and functional investigation of human guanylate kinase reveals allosteric networking and a crucial role for the enzyme in cancer.

  Khan N., Shah P.P., Ban D., Trigo-Mourino P., Carneiro M.G., DeLeeuw L., Dean W.L., Trent J.O., Beverly L.J., Konrad M., Lee D., Sabo T.M.

  Human guanylate kinase (hGMPK) is the only known enzyme responsible for cellular GDP production, making it essential for cellular viability and proliferation. Moreover, hGMPK has been assigned a critical role in metabolic activation of antiviral and antineoplastic nucleoside-analog prodrugs. Given ... >> More

  Human guanylate kinase (hGMPK) is the only known enzyme responsible for cellular GDP production, making it essential for cellular viability and proliferation. Moreover, hGMPK has been assigned a critical role in metabolic activation of antiviral and antineoplastic nucleoside-analog prodrugs. Given that hGMPK is indispensable for producing the nucleotide building blocks of DNA, RNA, and cGMP and that cancer cells possess elevated GTP levels, it is surprising that a detailed structural and functional characterization of hGMPK is lacking. Here, we present the first high-resolution structure of hGMPK in the apo form, determined with NMR spectroscopy. The structure revealed that hGMPK consists of three distinct regions designated as the LID, GMP-binding (GMP-BD), and CORE domains and is in an open configuration that is nucleotide binding-competent. We also demonstrate that nonsynonymous single-nucleotide variants (nsSNVs) of the hGMPK CORE domain distant from the nucleotide-binding site of this domain modulate enzymatic activity without significantly affecting hGMPK's structure. Finally, we show that knocking down the <i>hGMPK</i> gene in lung adenocarcinoma cell lines decreases cellular viability, proliferation, and clonogenic potential while not altering the proliferation of immortalized, noncancerous human peripheral airway cells. Taken together, our results provide an important step toward establishing hGMPK as a potential biomolecular target, from both an orthosteric (ligand-binding sites) and allosteric (location of CORE domain-located nsSNVs) standpoint. << Less

  J. Biol. Chem. 294:11920-11933(2019) [PubMed] [EuropePMC]

• Guanylate kinases from human erythrocytes, hog brain, and rat liver.

  Agarwal K.C., Miech R.P., Parks R.E. Jr.

  Methods Enzymol 51:483-490(1978) [PubMed] [EuropePMC]

• Guanylate kinase from Escherichia coli B.

  Oeschger M.P.

  Methods Enzymol 51:473-482(1978) [PubMed] [EuropePMC]

• Partial purification and properties of ATP:GMP phosphransferase from rat liver.

  Buccino R.J. Jr., Roth J.S.

  Arch Biochem Biophys 132:49-61(1969) [PubMed] [EuropePMC]