Gabaculine: γ-aminobutyrate aminotransferase inhibitor of microbial origin

Kobayashi, Kazuo; Miyazawa, Shigeru; Terahara, Akira; Mishima, Hiroshi; Kurihara, Hideshi

doi:10.1016/s0040-4039(00)77904-4

Cited by 56 publications

(14 citation statements)

References 3 publications

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“…Recently, an inhibitor structure of the (R)-ATA from Nectria haematococca (PDB code: 4CMF) was published by the Littlechild group [25]. The sequence identity of this transaminase to the here-reported enzyme is 69.1%.…”

Section: Discussionmentioning

confidence: 84%

Structural and biochemical characterization of the dual substrate recognition of the (R)‐selective amine transaminase from Aspergillus fumigatus

et al. 2014

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Chiral amines are important precursors for the pharmaceutical and finechemical industries. Because of this, the demand for enantiopure amines is currently increasing. Amine transaminases can produce a large spectrum of chiral amines in the (R)-or (S)-configuration, depending on their substrate scope and stereo-preference, by converting a prochiral ketone into the chiral amine while using alanine as the amine donor producing pyruvate as an a-keto acid product. In order to guide the protein engineering of transaminases to improve substrate specificity and enantioselectivity, we carried out a crystal structure analysis at 1.6A resolution of the (R)-amine transaminase from Aspergillus fumigatus with the bound inhibitor gabaculine. This revealed that Arg126 has an important role in the dual substrate recognition of this enzyme because mutating this residue to alanine reduced substantially the ability of the enzyme to use pyruvate as an amino acceptor. DatabaseCoordinates and structure factors have been deposited with the Protein Data Bank under accession code 4UUG.

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Section: Discussionmentioning

confidence: 84%

Structural and biochemical characterization of the dual substrate recognition of the (R)‐selective amine transaminase from Aspergillus fumigatus

et al. 2014

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“…Gabaculine (5-amino-1,3-cyclohexadienelcarboxylic acid), a naturally occurring amino acid isolated from Streptomyces toyocaenis (56), is an irreversible inhibitor of many PLP-requiring aminotransferases (57). Rinehart et al (58) and Ganem (59) had, in fact, suggested that this compound might be an intermediate on the biosynthetic pathway to mC 7 N units.…”

Section: -Amino-5-hydroxybenzoic Acid Synthasementioning

confidence: 99%

3-Amino-5-hydroxybenzoic Acid Synthase, the Terminal Enzyme in the Formation of the Precursor of mC7N Units in Rifamycin and Related Antibiotics

Kim

Fryhle

et al. 1998

Journal of Biological Chemistry

111

116

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The biosynthesis of ansamycin antibiotics, like rifamycin B, involves formation of 3-amino-5-hydroxybenzoic acid (AHBA) by a novel variant of the shikimate pathway. AHBA then serves as the starter unit for the assembly of a polyketide which eventually links back to the amino group of AHBA to form the macrolactam ring. The terminal enzyme of AHBA formation, which catalyzes the aromatization of 5-deoxy-5-amino-3-dehydroshikimic acid, has been purified to homogeneity from Amycolatopsis mediterranei, the encoding gene has been cloned, sequenced, and overexpressed in Escherichia coli. The recombinant enzyme, a (His) 6 fusion protein, as well as the native one, are dimers containing one molecule of pyridoxal phosphate per subunit. Mechanistic studies showed that the enzyme-bound pyridoxal phosphate forms a Schiff's base with the amino group of 5-deoxy-5-amino-3-dehydroshikimic acid and catalyzes both an ␣,␤-dehydration and a stereospecific 1,4-enolization of the substrate. Inactivation of the gene encoding AHBA synthase in the A. mediterranei genome results in loss of rifamycin formation; production of the antibiotic is restored when the mutant is supplemented with AHBA.

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“…-Allylamines and their derivatives are important intermediates in organic synthesis, and many of them show biological activity as antimycotics like naftifine [ 11,, and 1-aminocycloalk-2-enes [3], as neurotoxins like gabaculine [4], as antibiotics like oryzoxymycin [5], and as compounds with potential antiviral activity like dideoxynucleosides [6] as e.g. cytosimine [7], neplanocine [8], and carbovir [9].…”

Section: Asymmetric Catalysis Bymentioning

confidence: 99%

“…3440m,3030w, 3005m, 3000m, 2985m,2940m, 2860w, 1710s, 1610w, 15003, 1370m, 1240w, 1170s, 1100~~. 29 (22) (4).…”

Section: Merhyl8-azubicyclo(si0]octane-8-carboxylate (Ic)mentioning

confidence: 99%

Asymmetric Catalysis by Vitamin B₁₂: The Isomerization of Achiral Aziridines to Optically Active Allylic Amines

Zhang

Scheffold

1993

Helvetica Chimica Acta

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Achiral N-acylaziridines are isomerized to optically active N-acyl-allylamines in eels of up to 95 % by catalytic amounts of cob (1) The synthesis of primary allylamines has been reviewed in [lo]. Recent related work concerns mainly the enantioselective allylic amination of cis-alkenes by chiral N-sulfinylcarbamates [l 11, of alkynes with chiral Zr-derived reagents [12], and of allylic carbonates with chiral Pd complexes [ 131 and the enantioselective aziridination of olefins catalyzed by chiral transition-metal complexes [ 141.As an extension of our previous work on the enantioselective isomerization of epoxides to allylic alcohols [15], we report here on the cob(1)alamin-catalyzed conversion of achiral N-acylaziridines 1 to optically active (R)-N-acyI(cycloalk-2-en-l -yl)amines 2 (Scheme 1).

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Gabaculine: γ-aminobutyrate aminotransferase inhibitor of microbial origin

Cited by 56 publications

References 3 publications

Structural and biochemical characterization of the dual substrate recognition of the (R)‐selective amine transaminase from Aspergillus fumigatus

Structural and biochemical characterization of the dual substrate recognition of the (R)‐selective amine transaminase from Aspergillus fumigatus

3-Amino-5-hydroxybenzoic Acid Synthase, the Terminal Enzyme in the Formation of the Precursor of mC7N Units in Rifamycin and Related Antibiotics

Asymmetric Catalysis by Vitamin B₁₂: The Isomerization of Achiral Aziridines to Optically Active Allylic Amines

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Gabaculine: γ-aminobutyrate aminotransferase inhibitor of microbial origin

Cited by 56 publications

References 3 publications

Structural and biochemical characterization of the dual substrate recognition of the (R)‐selective amine transaminase from Aspergillus fumigatus

Structural and biochemical characterization of the dual substrate recognition of the (R)‐selective amine transaminase from Aspergillus fumigatus

3-Amino-5-hydroxybenzoic Acid Synthase, the Terminal Enzyme in the Formation of the Precursor of mC7N Units in Rifamycin and Related Antibiotics

Asymmetric Catalysis by Vitamin B12: The Isomerization of Achiral Aziridines to Optically Active Allylic Amines

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Asymmetric Catalysis by Vitamin B₁₂: The Isomerization of Achiral Aziridines to Optically Active Allylic Amines