Substrates: Difference between revisions
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In a ''substrate reduction therapy'' a small molecule inhibitor ([[Acid beta-glucosidase with N-nonyl-deoxynojirimycin|Zavesca™]]) is used to inhibit the synthesis of the accumulated glucosylceramide. | In a ''substrate reduction therapy'' a small molecule inhibitor ([[Acid beta-glucosidase with N-nonyl-deoxynojirimycin|Zavesca™]]) is used to inhibit the synthesis of the accumulated glucosylceramide. | ||
NADH quinone oxidoreductase (NQO1) substrates | '''NADH quinone oxidoreductase (NQO1) substrates''' | ||
Quinones (including duroquinone (2,3,5,6-tetramethyl-''p''-benzoquinone) are substrates of NQO1 (it catalyzes two-electron reduction of them to hydroquinones). Duroquinone <font color='black'><b>(yellow)</b></font> binds to the <scene name='2f1o/Align1/4'>active site</scene> by interactions involving the FAD and several hydrophobic and hydrophilic residues in the duroquinone-NQO1 complex ([[1dxo]]). | Quinones (including duroquinone (2,3,5,6-tetramethyl-''p''-benzoquinone) are substrates of NQO1 (it catalyzes two-electron reduction of them to hydroquinones). Duroquinone <font color='black'><b>(yellow)</b></font> binds to the <scene name='2f1o/Align1/4'>active site</scene> by interactions involving the FAD and several hydrophobic and hydrophilic residues in the duroquinone-NQO1 complex ([[1dxo]]). | ||
Revision as of 18:10, 14 October 2021
Under construction! AChE substrate Solution of the three-dimensional (3D) structure of Torpedo californica acetylcholinesterase (TcAChE) in 1991 [1] opened up new horizons in research on an enzyme that had already been the subject of intensive investigation. The unanticipated structure of this extremely rapid enzyme, in which the active site was found to be buried at the bottom of a , lined by (colored dark magenta), led to a revision of the views then held concerning substrate traffic, recognition and hydrolysis [2]. This led to a series of theoretical and experimental studies, which took advantage of recent advances in theoretical techniques for treatment of proteins, such as molecular dynamics and electrostatics and to site-directed mutagenesis, utilizing suitable expression systems. Acetylcholinesterase hydrolysizes the neurotransmitter acetylcholine , producing group. ACh directly binds (via its nucleophilic Oγ atom) within the (ACh/TcAChE structure 2ace). The residues are also important in the ligand recognition [3]. After this binding acetylcholinesterase ACh. Drug Metabolism by CYP450 Enzymes Malarial Dihydrofolate Reductase as Drug Target In a substrate reduction therapy a small molecule inhibitor (Zavesca™) is used to inhibit the synthesis of the accumulated glucosylceramide. NADH quinone oxidoreductase (NQO1) substrates Quinones (including duroquinone (2,3,5,6-tetramethyl-p-benzoquinone) are substrates of NQO1 (it catalyzes two-electron reduction of them to hydroquinones). Duroquinone (yellow) binds to the by interactions involving the FAD and several hydrophobic and hydrophilic residues in the duroquinone-NQO1 complex (1dxo).
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ReferencesReferences
- ↑ Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, Silman I. Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science. 1991 Aug 23;253(5022):872-9. PMID:1678899
- ↑ Botti SA, Felder CE, Lifson S, Sussman JL, Silman I. A modular treatment of molecular traffic through the active site of cholinesterase. Biophys J. 1999 Nov;77(5):2430-50. PMID:10545346
- ↑ Raves ML, Harel M, Pang YP, Silman I, Kozikowski AP, Sussman JL. Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A. Nat Struct Biol. 1997 Jan;4(1):57-63. PMID:8989325