TY - JOUR
T1 - New tryptophanase inhibitors
T2 - Towards prevention of bacterial biofilm formation
AU - Scherzer, Roni
AU - Gdalevsky, Garik Y.
AU - Goldgur, Yehuda
AU - Cohen-Luria, Rivka
AU - Bittner, Shmuel
AU - Parola, Abraham H.
N1 - Funding Information:
We thank Dr. Yana Sotovsky for her helpful synthesis discussions. We are grateful for Prof. Yuri Torchinsky for introducing Tnase into our laboratory. This work was supported in part by the James Frank foundation, to AHP.
PY - 2009/4/1
Y1 - 2009/4/1
N2 - Tryptophanase (tryptophan indole-lyase, Tnase, EC 4.1.99.1), a bacterial enzyme with no counterpart in eukaryotic cells, produces from L-tryptophan pyruvate, ammonia and indole. It was recently suggested that indole signaling plays an important role in the stable maintenance of multicopy plasmids. In addition, Tnase was shown to be capable of binding Rcd, a short RNA molecule involved in resolution of plasmid multimers. Binding of Rcd increases the affinity of Tnase for tryptophan, and it was proposed that indole is involved in bacteria multiplication and biofilm formation. Biofilm-associated bacteria may cause serious infections, and biofilm contamination of equipment and food, may result in expensive consequences. Thus, optimal and specific factors that interact with Tnase can be used as a tool to study the role of this multifunctional enzyme as well as antibacterial agents that may affect biofilm formation. Most known quasi-substrates inhibit Tnase at the mM range. In the present work, the mode of Tnase inhibition by the following compounds and the corresponding Ki values were: S-phenylbenzoquinone-L-tryptophan, uncompetitively, 101 μM; α-amino-2-(9,10-anthraquinone)-propanoic acid, noncompetitively, 174 μM; L-tryptophane-ethylester, competitively, 52 μM; N-acetyl-L-tryptophan, noncompetitively, 48 μM. S-phenylbenzoquinone-L- tryptophan and α-amino-2-(9,10-anthraquinone)-propanoic acid were newly synthesized.
AB - Tryptophanase (tryptophan indole-lyase, Tnase, EC 4.1.99.1), a bacterial enzyme with no counterpart in eukaryotic cells, produces from L-tryptophan pyruvate, ammonia and indole. It was recently suggested that indole signaling plays an important role in the stable maintenance of multicopy plasmids. In addition, Tnase was shown to be capable of binding Rcd, a short RNA molecule involved in resolution of plasmid multimers. Binding of Rcd increases the affinity of Tnase for tryptophan, and it was proposed that indole is involved in bacteria multiplication and biofilm formation. Biofilm-associated bacteria may cause serious infections, and biofilm contamination of equipment and food, may result in expensive consequences. Thus, optimal and specific factors that interact with Tnase can be used as a tool to study the role of this multifunctional enzyme as well as antibacterial agents that may affect biofilm formation. Most known quasi-substrates inhibit Tnase at the mM range. In the present work, the mode of Tnase inhibition by the following compounds and the corresponding Ki values were: S-phenylbenzoquinone-L-tryptophan, uncompetitively, 101 μM; α-amino-2-(9,10-anthraquinone)-propanoic acid, noncompetitively, 174 μM; L-tryptophane-ethylester, competitively, 52 μM; N-acetyl-L-tryptophan, noncompetitively, 48 μM. S-phenylbenzoquinone-L- tryptophan and α-amino-2-(9,10-anthraquinone)-propanoic acid were newly synthesized.
KW - Indole
KW - Inhibition
KW - L-tryptophan
KW - Quasi-substrates
UR - http://www.scopus.com/inward/record.url?scp=68049086742&partnerID=8YFLogxK
U2 - 10.1080/14756360802187612
DO - 10.1080/14756360802187612
M3 - Article
C2 - 18608755
AN - SCOPUS:68049086742
SN - 1475-6366
VL - 24
SP - 350
EP - 355
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
IS - 2
ER -