Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.5.1.2 (DNA ligase)
 2,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MODEST RESULTS TILL NOW: Despite progress in the treatment of bronchial cancer (BC) over the last 20 years, notably with platinum-based chemotherapy, results in terms of survival have been modest and prognosis of the tumor generally remains unfavorable. CLASSICAL CHEMOTHERAPY: In non-small cell BC, 5 new cytotoxic agents: vinorelbine (a new mitotic inhibitor), gemcitabine (an antimetabolic), docetaxel and paclitaxel (of the taxane family), irinotecan (DNA repair enzyme inhibitor) have shown interesting results. In small cell BC, among the new cytotoxics, only topoisomerase I inhibitors represented by irinotecan and topotecan are really interesting. Taxanes appear rather disappointing. ONGOING CLINICAL ASSESSMENT OF NEW MOLECULES: Exploration of new drugs is an absolute priority. In parallel with the development of new traditional cytotoxics (trapazamin, oxaliplatin, ALIMTA a new antifolate, UFT and epothilone); studies on agents with biological or molecular effects: thyroxin-kinase inhibitors, trastuzumab--a monoclonal antibody--a metalloprotease inhibitor and marimastat are presently ongoing.
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PMID:[New drugs in bronchial cancer]. 1214 65

Small-insert metagenomic libraries from four samples were constructed by a topoisomerase-based and a T4 DNA ligase-based approach. Direct comparison of both approaches revealed that application of the topoisomerase-based method resulted in a higher number of insert-containing clones per microg of environmental DNA used for cloning and a larger average insert size. Subsequently, the constructed libraries were partially screened for the presence of genes conferring proteolytic activity. The function-driven screen was based on the ability of the library-containing Escherichia coli clones to form halos on skim milk-containing agar plates. The screening of 80,000 E. coli clones yielded four positive clones. Two of the plasmids (pTW2 and pTW3) recovered from positive clones conferred strong proteolytic activity and were studied further. Analysis of the entire insert sequences of pTW2 (28,113 bp) and pTW3 (19,956 bp) suggested that the DNA fragments were derived from members of the genus Xanthomonas. Each of the plasmids harbored one gene (2,589 bp) encoding a metalloprotease (mprA, pTW2; mprB, pTW3). Sequence and biochemical analyses revealed that MprA and MprB are similar extracellular proteases belonging to the M4 family of metallopeptidases (thermolysin-like family). Both enzymes possessed a unique modular structure and consisted of four regions: the signal sequence, the N-terminal proregion, the protease region, and the C-terminal extension. The architecture of the latter region, which was characterized by the presence of two prepeptidase C-terminal domains and one proprotein convertase P domain, is novel for bacterial metalloproteases. Studies with derivatives of MprA and MprB revealed that the C-terminal extension is not essential for protease activity. The optimum pH and temperature of both proteases were 8.0 and 65 degrees C, respectively, when casein was used as substrate.
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PMID:Isolation and characterization of metalloproteases with a novel domain structure by construction and screening of metagenomic libraries. 1921 12