Crystal structure of tryptophanase

Isupov, Michail N.; Antson, A.A.; Dodson, E.J.; Dodson, Guy; Dementieva, I.; Zakomirdina, Lyudmila N.; Wilson, K.S.; Dauter, Zbigniew; Лебедев, А. А.; Harutyunyan, E.H.

doi:10.1006/jmbi.1997.1561

Cited by 114 publications

(112 citation statements)

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“…The structure of E. coli apo enzyme was solved in two crystal forms [26,27] and the structure of a highly homologous Tnase from P. vulgaris was solved in the holo form [28]. The three structures hold significant deviations in the relative orientation of the 'large' and 'small' domains and, as a consequence, show variations in the width of the catalytic site cleft and the geometry of the cofactor binding site.…”

Section: Discussionmentioning

confidence: 99%

New tryptophanase inhibitors: Towards prevention of bacterial biofilm formation

Scherzer

Gdalevsky

Goldgur

et al. 2008

Journal of Enzyme Inhibition and Medicinal Chemistry

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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 mM; a-amino-2-(9,10-anthraquinone)-propanoic acid, noncompetitively, 174 mM; L-tryptophane-ethylester, competitively, 52 mM; N-acetyl-L-tryptophan, noncompetitively, 48 mM. S-phenylbenzoquinone-L-tryptophan and a-amino-2-(9,10-anthraquinone)-propanoic acid were newly synthesized.

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Section: Discussionmentioning

confidence: 99%

New tryptophanase inhibitors: Towards prevention of bacterial biofilm formation

Scherzer

Gdalevsky

Goldgur

et al. 2008

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…When K ϩ is replaced by Na ϩ , the activity of the enzyme drops 95% and the change in coordination within the loop causes the O␥ of Ser-80 to swing away and clash with the phenyl ring of Tyr-301 that reorients and compromises substrate binding. Likewise, in other PLP-dependent enzymes like Ser hydratase (28), tryptophanase (29), and tyrosinase (30), the K ϩ binding site makes no contact with substrate but helps organize the architecture of the active site.…”

Section: K ؉ -Activated Type II Enzymesmentioning

confidence: 99%

A Structural Perspective on Enzymes Activated by Monovalent Cations

2006

Journal of Biological Chemistry

121

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Enzymes activated by monovalent cations are abundantly represented in plants and the animal world. They have evolved to exploit Na ؉ and K ؉ , readily available in biological environments, as major driving forces for substrate binding and catalysis. Recent progress in the structural biology of such enzymes has answered long standing questions about the molecular mechanism of activation and the origin of monovalent cation selectivity. That enables a simple classification of these functionally diverse enzymes and reveals unanticipated connections with ion transporters.Over 60 years ago, Boyer et al.(1) reported in the pages of this Journal that pyruvate kinase would express appreciable catalytic activity only in the presence of K ϩ . A similar effect was soon discovered in other systems, and just a few decades later the field of enzymes requiring a monovalent cation (M ϩ ) for optimal activity encompassed hundreds of examples from plants and the animal world (2, 3). Since the beginning, this rapidly expanding field had to address two basic questions, namely the molecular mechanism of M ϩ activation and the structural basis of M ϩ selectivity. Because kinetic investigation would only provide indirect answers, further progress in the field had to await high resolution crystal structures of M ϩ -activated enzymes, which have become available only over the last decade.A classification of M ϩ -activated enzymes can be based on the selectivity of the effect, as established by kinetic studies, and the mechanism of activation, as shown from structural analysis. The effect has exquisite specificity, with Na ϩ

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“…We compared its crystal structure with three homologues, PLP-dependent enzymes whose crystal structures have been determined: Proteus vulgaris Trpase (PDB entry 1ax4 18 ), Citrobacter freundii tyrosine phenol lyase (PDB entry 1tpl 19 ), and E. coli aspartate amino transferase (PDB entry 1cq7).…”

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confidence: 99%

Structural insights into cold inactivation of tryptophanase and cold adaptation of subtilisin S41

et al. 2007

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A wide variety of enzymes can undergo a reversible loss of activity at low temperature, a process that is termed cold inactivation. This phenomenon is found in oligomeric enzymes such as tryptophanase (Trpase) and other pyridoxal phosphate dependent enzymes. On the other hand, cold‐adapted, or psychrophilic enzymes, isolated from organisms able to thrive in permanently cold environments, have optimal activity at low temperature, which is associated with low thermal stability. Since cold inactivation may be considered “contradictory” to cold adaptation, we have looked into the amino acid sequences and the crystal structures of two families of enzymes, subtilisin and tryptophanase. Two cold adapted subtilisins, S41 and subtilisin‐like protease from Vibrio, were compared to a mesophilic and a thermophilic subtilisins, as well as to four PLP‐dependent enzymes in order to understand the specific surface residues, specific interactions, or any other molecular features that may be responsible for the differences in their tolerance to cold temperatures. The comparison between the psychrophilic and the mesophilic subtilisins revealed that the cold adapted subtilisins have a high content of acidic residues mainly found on their surface, making it charged. The analysis of the Trpases showed that they have a high content of hydrophobic residues on their surface. Thus, we suggest that the negatively charged residues on the surface of the subtilisins may be responsible for their cold adaptation, whereas the hydrophobic residues on the surface of monomeric Trpase molecules are responsible for the tetrameric assembly, and may account for their cold inactivation and dissociation. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 354–359, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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Crystal structure of tryptophanase

Cited by 114 publications

References 89 publications

New tryptophanase inhibitors: Towards prevention of bacterial biofilm formation

New tryptophanase inhibitors: Towards prevention of bacterial biofilm formation

A Structural Perspective on Enzymes Activated by Monovalent Cations

Structural insights into cold inactivation of tryptophanase and cold adaptation of subtilisin S41

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