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A’-3-Ketosteroid isomerase

Steroid Systems Labeling of steroid systems, 46, 447 irreversible inhibitors of A -3-ketosteroid isomerase acetylenic and allenic 3-0X0-5,10-secosteroids, 46, 461 labeling of AC3-ketosteroid isomerase by photoexcited steroid ketones, 46, 469. [Pg.39]

This enzyme [EC 5.3.3.1], also called steroid A-isomerase and A -3-ketosteroid isomerase, catalyzes the interconversion of a 3-oxo-A -steroid and a 3-oxo-A -steroid. [Pg.397]

A 3-Ketosteroid isomerase (3-KSI). This enz)mie catalyses the allylic isomerization of the 5,6 double bond of A5-3-ketosteroids to the 4,5 position by stereospecific intramolecular transfer of a proton. The enz)mie has been isolated from bacteria, and especially the 3-KSIs from Comamoms testosteroni and Pseudomonas putida have been investigated (Smith et al, 1980). The gene coding for the 3-KSI of Pseudomonas putida biot) e B has been cloned and its nucleotide sequence determined (Kim et al, 1994). [Pg.325]

Chloro-9-cyclopentyl-8-azapurine inhibited synthesis of DNA, RNA, and protein in E. coli. Blockage of thymine-nucleotide formation was the first effect seen. Alkylation of enzymes by the 6-chloro substituent was suggested as a mechanism. This azapurine inhibited the RNA polymerase from E. coli, but not that from M. lysodeikticus. Formyltetrahydrofolate synthetases, of both mammalian and bacterial origins, were strongly inhibited. The same azapurine, at 0.3 mM, markedly inhibited the steroid-induced synthesis of A -3-ketosteroid isomerase in Pseudomonas testoster-oni ... [Pg.175]

K. S. Kim, W. Lee, K. Y. Choi, and B.-H. Oh, Crystal structure of delta A -3-ketosteroid isomerase from pseudomonas testosteroni in complex with equilenin settles the correct hydrogen bonding scheme for transition state stabilization, J. Biol. Chem. 274, 32863-32868 (1999). (e) T. K. Manojkumar, C. Cui, and K. S. Kim, Theoretical insights into the mechanism of acetylcholinesterase-catalyzed acylation of acetylcholine, J. Comput. Chem. 26, 606-611... [Pg.191]

Benson, A. M., Talalay, P., Keen, J. H., and Jakoby, W. B., Relationship between the soluble glutathione-dependent A -3-ketosteroid isomerase and the glutathione S-transferases of the liver. Proc. Natl. Acad. Sci. U SA. 74, 158-162 (1977). [Pg.361]

Of the three isomerases, A- -3-ketosteroid isomerase P. testosteroni) has received the greatest experimental attention in recent years, revealing some intrigu-... [Pg.353]

Fig. 5. Proposed mechanism for A -3-ketosteroid isomerase consistent with NMR, X-ray, and stereochemical data, as well as with the results of site-directed mutagenesis (/26, 127). Fig. 5. Proposed mechanism for A -3-ketosteroid isomerase consistent with NMR, X-ray, and stereochemical data, as well as with the results of site-directed mutagenesis (/26, 127).
Irreversible Inhibitors of A -3-Ketosteroid Isomerase Acetylenic and Allenic 3-Oxo-5,10-secosteroids... [Pg.461]

Based on the proposed molecular mechanism of this reaction, a series of acetylenic 5,10-secosteroids has been prepared in the belief that they might serve as substrates for A -3-ketosteroid isomerase. Abstraction of the proton at C-4 by the enzyme should then generate, via an enolic intermediate, the corresponding highly reactive conjugated allenic ketones, which might be expected to react covalently with a nucleophilic amino acid residue at the active site (Scheme 3). This proposal was based on expected conformational similarities between the acetylenic 5,10-seoo-steroids and the normal A -S-ketosteroid substrates for the enzyme. [Pg.462]

Measurement of Rates of Inhibition. The inhibition of A -3-keto-steroid isomerase activity has been studied in systems containing in a final volume of 500 /il 1 mAf potassium phosphate at pH 7.0/ 5-8 pM crystalline A -3-ketosteroid isomerase of P. testosteroni, and 10-200 pM allenic or acetylenic steroid (steroid added in 20 jal of 1,4-dioxane). The reactions were run at 25° in small polypropylene tubes containing a... [Pg.463]

Fia. 1. Irreversible inactivation of A -3-ketosteroid isomerase by 5,10-secoestr-6-yne-3,10,17-trione (O) or 5,10-seco-19-norpregn-5-yne-3,10,20-trione ( ). Double reciprocal plots are shown of the apparent pseudo-first-order rate constant of inactivation (fcapp) with respect to inhibitor concentration. Values of Ki and k, were determined from slopes and intercepts. [F. H. Batzold and C. H. Robinson, J. Am. Chem. Soc. 97, 2576 (1975)]. [Pg.466]

Cyclodec-5-yn-l-one cyclizes when treated with BF3 or AICI3 to give bicyclo-[4,4,0]dec-l(6)-en-2 One. The acetylenic steriod analogues (133 R = O a—H, P—MeCO) rapidly and irreversibly inhibit bacterial A -3-ketosteroid isomerase possibly via isomerization to the conjugated allene. ... [Pg.248]

Fig. 6.8 Residues in the active site of A -3-ketosteroid isomerase from Escherichia colt [111]. Aspartic acid (D) residues 38 and 99, tyrosines (7) 14, 30 and 55, and atoms 3-6 of a bound steroid substrate are labeled. (Add 2 to the residue numbers to get those in the widely studied enzyme from Pseudomonas piaida.) Dotted lines indicate likely hydrogen htnids. The enzyme catalyzes rearrangement of the C5-C6 double bond to C4-C5 by facilitating enolization of the keto group and transfer of a proton from C4 to C6, probably via D38. The shifted C=0 stretching frequencies of bound 19-norleslosleione point to a stnaig local electric field that favors the enolization [106]... Fig. 6.8 Residues in the active site of A -3-ketosteroid isomerase from Escherichia colt [111]. Aspartic acid (D) residues 38 and 99, tyrosines (7) 14, 30 and 55, and atoms 3-6 of a bound steroid substrate are labeled. (Add 2 to the residue numbers to get those in the widely studied enzyme from Pseudomonas piaida.) Dotted lines indicate likely hydrogen htnids. The enzyme catalyzes rearrangement of the C5-C6 double bond to C4-C5 by facilitating enolization of the keto group and transfer of a proton from C4 to C6, probably via D38. The shifted C=0 stretching frequencies of bound 19-norleslosleione point to a stnaig local electric field that favors the enolization [106]...
Austin, J.C., Kuliopulos, A., Mildvan, A.S., Spiro, T.G. Substrate polarization by residues in A -3-ketosteroid isomerase probed by site-directed mutagenesis and UV resonance Raman spectroscopy. Protein Sci. 1, 259-270 (1992)... [Pg.322]


See other pages where A’-3-Ketosteroid isomerase is mentioned: [Pg.561]    [Pg.378]    [Pg.326]    [Pg.1542]    [Pg.561]    [Pg.100]    [Pg.177]    [Pg.191]    [Pg.287]    [Pg.289]    [Pg.687]    [Pg.310]    [Pg.353]    [Pg.38]    [Pg.465]    [Pg.469]    [Pg.469]    [Pg.476]    [Pg.477]    [Pg.766]    [Pg.316]    [Pg.324]    [Pg.224]    [Pg.295]   


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