02563nas a2200265   4500008004100000022001400041245011100055210006900166260007900235300001400314490000700328520157900335653002901914653001801943653002501961653002301986653002202009653002802031100001802059700002102077700001902098700003302117700001902150856012802169       2007                        eng d  a0141-022900aTryptophan residue is identified in the substrate binding of penicillin G acylase from Kluyvera citrophila0 aTryptophan residue is identified in the substrate binding of pen  a360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USAbELSEVIER SCIENCE INCcAPR  a1389-13970 v403 a<p>Penicillin acylases are important enzymes in pharmaceutical industry for the production of semi-synthetic beta-lactam antibiotics via the key intermediate 6-aminopenicillanic acid. The penicillin G acylase purified from Kluyvera citrophila (KcPGA) on modification with tryptophan-specific reagents such as N-bromo succinamide (NBS) and 2-hydroxy 5-nitrobenzylbromide (HNBB) showed partial loss of activity and substrate protection. Various solute quenchers and substrate were used to probe the microenvironment of the putative reactive tryptophan through fluorescence quenching. Homology modeling of KcPGA structure has been carried out. Docking substrate on this modeled KcPGA structure identifies the tryptophan residue that is directly influenced by substrate binding. To confirm the biological significance of this particular tryptophan, we did a sequence comparison of PGAs from various organisms. The sequence alignment clustered the matches into two sets, those closer to (&gt; 40% identical) KcPGA and had the tryptophan of interest present in them formed the first set, while those less identical (&lt; 30%) to KcPGA and the particular tryptophan absent in them formed the second set. It is clear from the reported kinetic parameters of representative members of these two sets that the affinity for penicillin G (penG) of the former class is several times better. Thus, based on our studies we suggest that the tryptophan residue in the identified position is important for binding substrate penG by the acylases. (c) 2006 Elsevier Inc. All rights reserved.</p>10afluorescence measurement10aK. citrophila10aPenicillin G acylase10asequence alignment10asubstrate-docking10atryptophan modification1 aKumar, Suresh1 aPrabhune, Asmita1 aPundle, A., V.1 aKarthikeyan, Muthukumarasamy1 aSuresh, C., G.  uhttps://library.ncl.res.in/content/tryptophan-residue-identified-substrate-binding-penicillin-g-acylase-kluyvera-citrophila02253nas a2200181   4500008004100000022001400041245014600055210006900201260009100270300002900361490000700390520147700397100001601874700001901890700001901909700001901928856012401947       2016                        eng d  a1932-620300aTwo chitotriose-specific lectins show anti-angiogenesis, induces caspase-9-mediated apoptosis and early arrest of pancreatic tumor cell cycle0 aTwo chitotriosespecific lectins show antiangiogenesis induces ca  a1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USAbPUBLIC LIBRARY SCIENCEcJAN  aArticle Number: e01461100 v113 a<p>The antiproliferative activity of two chito-specific agglutinins purified from Benincasa hispida (BhL) and Datura innoxia (DiL9) of different plant family origin was investigated on various cancer cell lines. Both lectins showed chitotriose specificity, by inhibiting lectin hemagglutinating activity. On further studies, it was revealed that these agglutinins caused remarkable concentration-dependent antiproliferative effect on human pancreatic cancerous cells but not on the normal human umbilical vein endothelial cells even at higher doses determined using MTT assay. The GI(50) values were approximately 8.4 mu g ml(-1) (0.247 mu M) and 142 mu g ml(-1) (14.8 mu M) for BhL and DiL9, respectively, against PANC-1 cells. The growth inhibitory effect of these lectins on pancreatic cancer cells were shown to be a consequence of lectin cell surface binding and triggering G(0)/G(1) arrest, mitochondrial membrane depolarization, sustained increase of the intracellular calcium release and the apoptotic signal is amplified by activation of caspases executing cell death. Interestingly, these lectins also showed anti-angiogenic activity by disrupting the endothelial tubulogenesis. Therefore, we report for the first time two chito-specific lectins specifically binding to tumor glycans; they can be considered to be a class of molecules with antitumor activity against pancreatic cancer cells mediated through caspase dependent mitochondrial apoptotic pathway.</p>1 aSingh, Ruby1 aNawale, Laxman1 aSarkar, Dhiman1 aSuresh, C., G.  uhttps://library.ncl.res.in/content/two-chitotriose-specific-lectins-show-anti-angiogenesis-induces-caspase-9-mediated-1