CLONING, CHARACTERIZATION, AND MODELING OF MOUSE AND HUMAN GUANYLATE KINASES

Guanylate kinase catalyzes the phosphorylation of either GMP to GDP or dGMP to dGDP and is an essential enzyme in nucleotide metabolism path ways, Despite its involvement in antiviral drug activation in humans a nd in mouse model systems and as a target for chemotherapy, the human and mouse primary structures have never been elucidated, Full-length c DNA clones encoding enzymatically active guanylate kinase were isolate d from mouse B-cell lymphoma and human peripheral blood lymphocyte cDN A libraries, Multiple tissue Northern blots demonstrated an mRNA speci es of approximately 1 kilobase for both mice and humans in all tissue types examined, The mouse cDNA is predicted to encode a 198-amino acid protein with a molecular mass of 21,904 daltons, The human cDNA is pr edicted to encode a 197-amino acid protein with a molecular mass of 21 ,696 daltons, These proteins share 88% sequence identity with each oth er and 52-54% identity with the yeast guanylate kinase. Molecular mode ling using the yeast diffraction coordinates indicates a high degree o f conservation within the active site and maintenance of the overall s tructural integrity, despite a lack of similarity along the periphery of the enzyme.