Kynureninases: Enzymological Properties and Regulation Mechanism

Soda, Kenji; Tanizawa, Katsuyuki

doi:10.1002/9780470122945.ch1

Cited by 32 publications

(24 citation statements)

References 70 publications

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“…3 and 4) for a rare structural motif that matches exactly the 2F5 MPER epitope (Figs. 5 and 8); we conclude that the host antigen mimicked by the 2F5 MPER epitope is the H4 domain of KYNU, a ubiquitously expressed enzyme of tryptophan metabolism (Soda and Tanizawa, 1979).…”

Section: Discussionmentioning

confidence: 85%

Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies

Yang

Holl

Liu

et al. 2013

Journal of Experimental Medicine

169

312

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Section: Discussionmentioning

confidence: 85%

Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies

Yang

Holl

Liu

et al. 2013

Journal of Experimental Medicine

169

312

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“…For energy production, kynureninase, and glycerol kinase are upregulated in FB. Kynureninase functions in the catabolic degradation of L-tryptophan to generate carbon, nitrogen and NAD (Soda and Tanizawa, 1979). Glycerol is the main compatible solute used by yeast under salt stress (Neves et al, 2004), with glycerol kinase being the first enzyme in glycerol catabolism in Saccharomyces cerevisiae (Neves et al, 2004).…”

Section: Differentially Expressed Genes In Fbmentioning

confidence: 99%

Cataloging and profiling genes expressed in Lentinula edodes fruiting body by massive cDNA pyrosequencing and LongSAGE

Chum

Kwan

et al. 2011

Fungal Genetics and Biology

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“…Kynureninase ( l ‐kynurenine hydrolase, http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/7/1/3.html) is a pyridoxal‐5′‐phosphate (PLP)‐dependent enzyme that catalyzes the hydrolytic C β –C γ cleavage of l ‐kynurenine to alanine and anthranilic acid (Eqn 1) : …”

Section: Introductionmentioning

confidence: 99%

“…Kynureninase (L-kynurenine hydrolase, EC 3.7.1.3) is a pyridoxal-5′-phosphate (PLP)-dependent enzyme that catalyzes the hydrolytic C b -C c cleavage of L-kynurenine to alanine and anthranilic acid (Eqn 1) [1]: This is one of a small group of enzymes that catalyze a retro-Claisen reaction. The enzyme is part of the major eukaryotic pathway for tryptophan catabolism, and is also found in a number of bacteria.…”

Section: Introductionmentioning

confidence: 99%

The phosphate of pyridoxal‐5′‐phosphate is an acid/base catalyst in the mechanism of Pseudomonas fluorescens kynureninase

Phillips

Scott²,

Paulose

et al. 2014

The FEBS Journal

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Kynureninase (l‐kynurenine hydrolase, http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/7/1/3.html) catalyzes the hydrolytic cleavage of l‐kynurenine to l‐alanine and anthranilic acid. The proposed mechanism of the retro‐Claisen reaction requires extensive acid/base catalysis. Previous crystal structures showed that Tyr226 in the Pseudomonas fluorescens enzyme (Tyr275 in the human enzyme) hydrogen bonds to the phosphate of the pyridoxal‐5′‐phosphate (PLP) cofactor. This Tyr residue is strictly conserved in all sequences of kynureninase. The human enzyme complexed with a competitive inhibitor, 3‐hydroxyhippuric acid, showed that the ligand carbonyl O is located 3.7 Å from the phenol of Tyr275 (Lima, S., Kumar, S., Gawandi, V., Momany, C. & Phillips, R. S. (2009) J. Med. Chem. 52, 389–396). We prepared a Y226F mutant of P. fluorescens kynureninase to probe the role of this residue in catalysis. The Y226F mutant has approximately 3000‐fold lower activity than wild‐type, and does not show the pKa values of 6.8 on kcat and 6.5 and 8.8 on kcat/Km seen for the wild‐type enzyme (Koushik, S. V., Moore, J. A. III, Sundararaju, B. & Phillips, R. S. (1998) Biochemistry 37, 1376–1382). Wild‐type kynureninase shows a resonance at 4.5 ppm in 31P‐NMR, which is shifted to 5.0, 3.3 and 2.0 ppm when the potent inhibitor 5‐bromodihydrokynurenine is added. However, Y226F kynureninase shows resonances at 3.6 and 2.5 ppm, and no change in the peak position is seen when 5‐bromodihydrokynurenine is added. Taken together, these results suggest that Tyr226 mediates proton transfer between the substrate and the phosphate, which accelerates formation of external aldimine and gem‐diol intermediates. Thus, the phosphate of PLP acts as an acid/base catalyst in the mechanism of kynureninase.

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Kynureninases: Enzymological Properties and Regulation Mechanism

Cited by 32 publications

References 70 publications

Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies

Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies

Cataloging and profiling genes expressed in Lentinula edodes fruiting body by massive cDNA pyrosequencing and LongSAGE

The phosphate of pyridoxal‐5′‐phosphate is an acid/base catalyst in the mechanism of Pseudomonas fluorescens kynureninase

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