Substrates
From Proteopedia
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systems. [http://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase] [http://en.wikipedia.org/wiki/Hydrolysis hydrolysizes] the [http://en.wikipedia.org/wiki/Neurotransmitter neurotransmitter] [http://en.wikipedia.org/wiki/Acetylcholine acetylcholine] <scene name='2ace/Cv/2'>(ACh)</scene>, producing <scene name='2ace/Cv/3'>choline and an acetate</scene> group. ACh directly binds <scene name='22/22/Cv/1'>Ser200</scene> (via its [http://en.wikipedia.org/wiki/Nucleophile nucleophilic] Oγ atom) within the <scene name='2ace/Cv/5'>catalytic triad (Ser200, His440, and Glu327)</scene> (ACh/''Tc''AChE structure [[2ace]]). The residues <scene name='2ace/Cv/6'>Trp84 and Phe330</scene> are also important in the [http://en.wikipedia.org/wiki/Ligand ligand] recognition <ref name="Raves">PMID:8989325</ref>. After this binding acetylcholinesterase <scene name='2ace/Cv/7'>hydrolysizes</scene> ACh. | systems. [http://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase] [http://en.wikipedia.org/wiki/Hydrolysis hydrolysizes] the [http://en.wikipedia.org/wiki/Neurotransmitter neurotransmitter] [http://en.wikipedia.org/wiki/Acetylcholine acetylcholine] <scene name='2ace/Cv/2'>(ACh)</scene>, producing <scene name='2ace/Cv/3'>choline and an acetate</scene> group. ACh directly binds <scene name='22/22/Cv/1'>Ser200</scene> (via its [http://en.wikipedia.org/wiki/Nucleophile nucleophilic] Oγ atom) within the <scene name='2ace/Cv/5'>catalytic triad (Ser200, His440, and Glu327)</scene> (ACh/''Tc''AChE structure [[2ace]]). The residues <scene name='2ace/Cv/6'>Trp84 and Phe330</scene> are also important in the [http://en.wikipedia.org/wiki/Ligand ligand] recognition <ref name="Raves">PMID:8989325</ref>. After this binding acetylcholinesterase <scene name='2ace/Cv/7'>hydrolysizes</scene> ACh. | ||
| - | + | [[Drug Metabolism by CYP450 Enzymes]] | |
| - | + | [[Malarial Dihydrofolate Reductase as Drug Target]] | |
| - | + | 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 | ||
| + | |||
| + | 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]]). | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 13:34, 13 October 2021
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References
- ↑ 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
