Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe the purification, cloning, and characterization of the CCA-adding enzyme [ATP(CTP):tRNA nucleotidyl transferase] from the thermophilic archaebacterium, Sulfolobus shibatae. Characterization of an archaeal CCA-adding enzyme provides formal proof that the CCA-adding activity is present in all three contemporary kingdoms. Antibodies raised against recombinant, expressed Sulfolobus CCA-adding enzyme reacted specifically with the 48-kDa protein and fully depleted all CCA-adding activity from S. shibatae crude extract. Thus, the cloned cca gene encodes the only CCA-adding activity in S. shibatae. Remarkably, the archaeal CCA-adding enzyme exhibits no strong homology to either the eubacterial or eukaryotic CCA-adding enzymes. Nonetheless, it does possess the active site signature G[SG][LIVMFY]xR[GQ]x5,6D[LIVM][CLIVMFY]3-5 of the nucleotidyltransferase superfamily identified by Holm and Sander (1995, Trends Biochem Sci 20:345-347) and sequence comparisons show that all known CCA-adding enzymes and poly(A) polymerases are contained within this superfamily. Moreover, we propose that the superfamily can now be divided into two (and possibly three) subfamilies: class I, which contains the archaeal CCA-adding enzyme, eukaryotic poly(A) polymerases, and DNA polymerase beta; class II, which contains eubacterial and eukaryotic CCA-adding enzymes, and eubacterial poly(A) polymerases; and possibly a third class containing eubacterial polynucleotide phosphorylases. One implication of these data is that there may have been intraconversion of CCA-adding and poly(A) polymerase activities early in evolution.
 ...
PMID:CCA-adding enzymes and poly(A) polymerases are all members of the same nucleotidyltransferase superfamily: characterization of the CCA-adding enzyme from the archaeal hyperthermophile Sulfolobus shibatae. 880 16

We present here computer generated model of N-terminal fragment, amino acids (aa) 36-245, of a Plasmodium vivax heat shock metalloprotease called PVHSP28, whose gene was cloned and characterised earlier. The fragment showed homology with HSPs from many organisms, including Escherichia coli and Haemophilus influenzae. PVHSP28 had the signature sequence 'HEXXH' and 'EXXXD' of Zinc metalloproteases. Being the first malarial HSP possessing metalloprotease activity, PVHSP28 is an ideal target for the design of new anti-malarial drugs. However, except for a small region (aa 62-132) which had 24.6% sequence similarity with 1TAQ (a DNA polymerase), it did not show sequence similarity with any published structures in protein data bank. Hence it could not be modelled using any automated modeling programs. We modelled 36-245 aa of PVHSP28 using predicted secondary structure as well as experimentally determined and predicted properties of the protein on the basis of its amino acid sequence, using various Internet tools and in-house package MODEL. The model was energy minimised using Sander's module of AMBER 5.0, working on a Silicon Graphics machine, with all atom force field.
 ...
PMID:Computer modeling of small heat-shock metalloprotease of the human malaria parasite Plasmodium vivax. 1169 26